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1.
Mem. Inst. Oswaldo Cruz ; 116: e200560, 2021. graf
Article in English | LILACS | ID: biblio-1154882

ABSTRACT

BACKGROUND Anisakis simplex antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) in mice. OBJECTIVES To study the capacity of DCs stimulated with A. simplex excretory-secretory (ES) or crude extract (CE) to generate Tregs. To investigate in vitro effects of antigens on the metabolic activity of splenocytes induced by LPS or CpG. METHODS Phenotypic and functional characterization of T cells co-cultured with A. simplex-pulsed DCs was performed by flow cytometry. Lymphocyte mitochondrial respiratory activity was estimated by the Alamar Blue® Assay. FINDINGS In C57BL/6J, CD4+CD25-Foxp3+ and CD8+CD25-Foxp3+ populations increased by CE-stimulated-DCs. In BALB/c, CE-stimulated-DCs caused the expansion of CD4+CD25+Foxp3+IL-10+ and CD8+CD25+Foxp3+IL-10+. IFN-γ expression raised in BALB/c CD4+CD25+ and CD4+CD25- for CE and ES, respectively. ES-stimulated-DCs increased CD4+CD25+ Foxp3+ and CD8+CD25- Foxp3+ expression in T cells. The association of ES or CE with LPS produced the increase in splenocyte activity in C57BL/6J. The association of CE with CpG decreased the proliferation caused by CpG in C57BL/6J. MAIN CONCLUSIONS A. simplex increase the frequency of Tregs, which in turn produce IL-10 and IFN-γ. The host genetic base is essential in the development of anti-Anisakis immune responses (Th2, Th1, Treg).


Subject(s)
Animals , Mice , Anisakis , T-Lymphocytes, Regulatory , Antigens/metabolism , Bone Marrow , Dendritic Cells , Forkhead Transcription Factors , Interleukin-2 Receptor alpha Subunit , Larva , Mice, Inbred BALB C , Mice, Inbred C57BL
2.
Braz. j. med. biol. res ; 54(9): e11062, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249335

ABSTRACT

Dendritic cells (DCs) play a crucial role as central orchestrators of immune system response in atherosclerosis initiation and progression. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the immune maturation of DCs, but the underlying mechanisms remain unclear. We isolated mouse bone marrow progenitors and stimulated them with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 to induce immature DCs. We then treated DCs with oxidized low-density lipoprotein (oxLDL) to induce maturation. LOX-1 siRNA was used to investigate the modulation of LOX-1 on the development of DCs and the underlying signal pathways. CD11c-positive DCs were successfully derived from mouse bone marrow progenitors. OxLDL promoted the expressions of DCs maturation markers and pro-inflammatory cytokines. OxLDL also upregulated LOX-1 expression and activated MAPK/NF-κB pathways. LOX-1 siRNA could attenuate the expression of MAPK/NF-κB pathways and inflammatory cytokines. In conclusion, oxLDL induced the maturation of DCs via LOX-1-mediated MAPK/NF-κB pathway, which contributed to the initiation and progression of atherosclerosis.


Subject(s)
Animals , Rats , Dendritic Cells , NF-kappa B , MAP Kinase Signaling System , Scavenger Receptors, Class E , Lipoproteins, LDL
3.
Article in Chinese | WPRIM | ID: wpr-828853

ABSTRACT

OBJECTIVE@#To investigate the changes in the exosomes secreted by mouse dendritic cell line DC2.4 after infection with and to analyze the possible regulatory mechanisms underlying such changes.@*METHODS@#The exosomes were extracted by ultracentrifugation from DC2.4 cells at 28 h after infection with . The morphology of the exosomes was examined with transmission electron microscopy, and the exosome size and density were determined using a nanoparticle tracker. High-throughput sequencing was carried out to identify the differentially expressed small RNAs in the exosomes derived from the infected cells.@*RESULTS@# infection resulted in a significantly increased density of exosomes secreted by DC2.4 cells. Small RNA sequencing revealed that infection caused an increase in the number of miRNAs and piRNAs in the exosomes. The significantly up-regulated piRNAs after the infection included piR-mmu-159, piR-mmu-1526, piR-mmu-9082, piR-mmu-17405, and piR-mmu-25576.@*CONCLUSIONS@# infection causes accumulation and enrichment of exosomes secreted by DC2.4 cells with increased miRNAs and piRNAs in the exosomes.


Subject(s)
Animals , Cell Line , Dendritic Cells , Exosomes , Mice , MicroRNAs , RNA, Small Interfering , Toxoplasma
4.
Article in English | WPRIM | ID: wpr-787139

ABSTRACT

We previously demonstrated that Bordetella bronchiseptica (B. bronchiseptica) antigen (Ag) enhances the Mycoplasma hyopneumoniae Ag-specific immune response. The focus of this study was whether acellular bacterin of B. bronchiseptica could be used as an adjuvant to increase antigen-presenting capability of dendritic cells (DCs) by increasing the level of activation. The metabolic activity of DCs was increased by B. bronchiseptica, similar to lipopolysaccharide (LPS). Flow cytometry analysis revealed that B. bronchiseptica increases the expression of major histocompatibility complex class-2, cluster of differentiation (CD)40, CD54, and CD86 which are closely related to DC-mediated immune responses. B. bronchiseptica enhanced the production of cytokines related to adaptive immune responses. Furthermore, the survival rate of B. bronchiseptica-injected groups was 100% at 15 and 20 mg/kg doses, whereas that of LPS-injected groups was only 20%, 0% at 15 and 20 mg/kg doses respectively, and so B. bronchiseptica is likely to be safer than LPS. Taken together, these results indicate that B. bronchiseptica can be used as an adjuvant to enhance the antigen-presenting capability of DCs. B. bronchiseptica is a candidate for producing vaccines, especially in case of DC-mediating efficacy and safety demands. This study provides researchers and clinicians with valuable information regarding the usage of B. bronchiseptica as a safe bacteria-derived immunostimulating agent for developing efficient vaccines.


Subject(s)
Bacterial Vaccines , Bordetella bronchiseptica , Bordetella , Cytokines , Dendritic Cells , Flow Cytometry , Immunization , Major Histocompatibility Complex , Mycoplasma hyopneumoniae , Survival Rate , Vaccines
5.
Article in English | WPRIM | ID: wpr-878349

ABSTRACT

Objective@#To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC).@*Methods@#DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 @*Results@#We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders.@*Conclusion@#In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.


Subject(s)
Adult , Aged , Cancer Vaccines/therapeutic use , China , Dendritic Cells/immunology , Female , Humans , Immunotherapy/methods , Injections, Intradermal , Male , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Viral Matrix Proteins/therapeutic use , Young Adult
6.
Article in English | WPRIM | ID: wpr-811060

ABSTRACT

PURPOSE: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs.METHODS: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization.RESULTS: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment.CONCLUSIONS: A reliable murine model of asthma by intravenous (i.v.) transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs.


Subject(s)
Adoptive Transfer , Anesthesia , Animals , Asthma , Cytokines , Dendritic Cells , Eosinophils , Goblet Cells , Humans , Immunoglobulin G , Immunoglobulins , Inflammation , Interleukin-13 , Lung , Methods , Mice , Models, Animal , Neutrophils , Ovalbumin , Ovum , T-Lymphocytes
7.
Braz. arch. biol. technol ; 63: e20180379, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132267

ABSTRACT

Abstract Hippocampus is a part of the brain that has a major role in spatial learning and memory which can be affected by herbal extracts. Incense resin (Styrax benzoin) has been used by local communities to improve intelligence. However, there is no scientific evidence of the functions of Styrax benzoin for regulating hippocampal function. The aim of this study was intended to analyze and investigate the effect of incense resin on learning, memory, and dendrite complexity of mice. Three months old male Deutch Democratic Yokohama (DDY) mice were injected orally with graded doses of 100, 150, and 200 mg/kg of incense resin aqueous extract daily for 30 days. Spatial learning and memory performance levels were tested with Y-maze alternation, novel object recognition, and Morris water maze. The branches and maximum dendritic span in the dentate gyrus were observed by the Golgi-Cox staining. Overall, our results showed that incense resin extract increased learning and memory ability, and the number of dendrite branching in the dentate gyrus.


Subject(s)
Animals , Male , Mice , Dendritic Cells/drug effects , Plant Extracts/pharmacology , Styrax/chemistry , Spatial Learning/drug effects , Memory/drug effects , Administration, Oral , Maze Learning/drug effects
8.
Braz. j. med. biol. res ; 53(4): e9282, 2020. graf
Article in English | LILACS | ID: biblio-1089351

ABSTRACT

Vitiligo is an acquired pigmentary disorder resulting from selective destruction of melanocytes. Emerging studies have suggested that T helper cell 17 (Th17) is potentially implicated in vitiligo development and progression. It was recently discovered that metabotropic glutamate receptor 4 (mGluR4) can modulate Th17-mediated adaptive immunity. However, the influence of mGluR4 on melanogenesis of melanocytes has yet to be elucidated. In the present study, we primarily cultured mouse bone marrow-derived dendritic cells (BMDC) and then knocked down and over-expressed mGluR4 using transfection. Transduced BMDC were co-cultured with CD4+ T cells and the expression of Th17-related cytokines were measured. The morphology and melanogenesis of B16 cells were observed after being treated with co-culture medium of CD4+ T cells and transduced BMDC. We found that mGluR4 knockdown did not affect the co-stimulatory CD80 and CD86 upregulation after lipopolysaccharide stimulation but did increase the expression of Th17-related cytokines, and further down-regulated the expression of microphthalmia-associated transcription factor (MITF) and the downstream genes, decreased melanin production, and destroyed the morphology of B16 cells. Conversely, over-expression of mGluR4 reduced the expression of CD80 and CD86, suppressed the production of Th17-related cytokines, increased the expression of MITF, and did not destroy the morphology of B16 cells. Our study confirmed that mGluR4 modulated the Th17 cell polarization and resulted in the alteration of melanogenesis and morphology of B16 cells. Collectively, these findings suggest mGluR4 might be a potent target involved in the immune pathogenesis of vitiligo.


Subject(s)
Animals , Male , Vitiligo/immunology , Dendritic Cells/cytology , Bone Marrow Cells/cytology , Cell Differentiation/physiology , Receptors, Metabotropic Glutamate/physiology , Th17 Cells/immunology , Vitiligo/genetics , RNA, Small Interfering/immunology , Th17 Cells/cytology , Flow Cytometry , Melanins/biosynthesis , Melanocytes/cytology , Mice, Inbred C57BL
9.
An. bras. dermatol ; 94(6): 747-750, Nov.-Dec. 2019. graf
Article in English | LILACS | ID: biblio-1054880

ABSTRACT

Abstract Melanoacanthoma is a rare variant of seborrheic keratosis, which is notable for dark pigmentation and fast radial growth, making it difficult to distinguish from melanoma. Histologically, it is characterized by proliferation of keratinocytes and dendritic melanocytes. The authors report a scalp lesion, fast growing, suspected by dermoscopy and confocal microscopy examination, with dendritic cells distributed throughout the lesion. Based on these findings, it was not possible to classify this lesion as clearly benign, so it was excised. Histopathologic evaluation and immunostain were consistent with melanoacanthoma.


Subject(s)
Humans , Male , Aged , Scalp Dermatoses/pathology , Skin Neoplasms/pathology , Keratosis, Seborrheic/pathology , Acanthoma/pathology , Dendritic Cells/pathology , Microscopy, Confocal/methods , Dermoscopy , Melanocytes/pathology
10.
Braz. dent. j ; 30(6): 617-625, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055455

ABSTRACT

Abstract The aim of this study was to determine if the distribution of Langerhans cells (LC) and interstitial dendritic cells (IDC) is altered in AIDS-associated oral Kaposi's sarcoma when compared to HIV-negative highly vascular oral lesions. Fifty-one cases of AIDS-associated oral Kaposi's sarcoma and 20 of highly vascular oral lesions were retrospectively retrieved. All cases of Kaposi's sarcoma were confirmed with immunoreactions against CD34 and HHV-8. Clinical data regarding sex, age and lesions location were obtained from pathology reports. Immunohistochemistry against CD207 (immature dendritic cells) and CD83 (mature dendritic cells) were done. LC were in the epithelium and IDC in the stroma. CD207+ cells predominated in the epithelium of the lesions, whereas CD83+ cells predominated in their stromal compartment. Kaposi's sarcoma had a lower CD207+ immature LC count (p=0.02) and an increased CD207+ IDC than highly vascular oral lesions (p<0.001). Moreover, Kaposi's sarcoma also showed an increased number of mature CD83+ IDC than highly vascular oral lesions (p<0.001). There were significant alterations in the distribution of LC and IDC in AIDS-associated Kaposi's sarcoma when compared to HIV-negative vascular oral lesions, suggesting that changes in their concentrations may play a role in the pathogenesis of Kaposi's sarcoma.


Resumo O objetivo deste estudo foi determinar se a distribuição das células de Langerhans (CL) e das células dendríticas intersticiais (CDI) está alterada no sarcoma de Kaposi oral associado à AIDS quando comparado às lesões orais altamente vasculares HIV-negativas. 51 casos de sarcoma de Kaposi oral associado à AIDS e 20 de lesões orais altamente vasculares foram recuperados retrospectivamente. Todos os casos de sarcoma de Kaposi foram confirmados pela positividade para os anticorpos CD34 e HHV-8. Dados clínicos sobre sexo, idade e localização das lesões foram obtidos dos laudos histopatológicos. Foram realizadas imunoistoquímica contra CD207 (células dendríticas imaturas) e CD83 (células dendríticas maduras). As CL estavam presentes no epitélio enquanto as CDI estavam presentes no estroma. As células CD207+ predominaram no epitélio das lesões, enquanto as células CD83+ predominaram no estroma. O sarcoma de Kaposi teve uma contagem mais baixa de CD imaturas CD207+ (p = 0,02) e número aumentado de CDC CD207+ do que lesões orais altamente vasculares (p<0,001). Além disso, o sarcoma de Kaposi também mostrou um número aumentado de CDI CD83+ maduras do que lesões orais altamente vasculares (p<0,001). Houve alterações significativas na distribuição de CL e CDI no sarcoma de Kaposi associado à AIDS quando comparado às lesões orais vasculares HIV-negativas, sugerindo que alterações na distribuição das mesmas podem desempenhar um papel na patogênese do sarcoma de Kaposi.


Subject(s)
Humans , Sarcoma, Kaposi , Acquired Immunodeficiency Syndrome , Herpesvirus 8, Human , Dendritic Cells , Retrospective Studies
11.
Arq. ciências saúde UNIPAR ; 23(2): 145-153, maio-ago. 2019.
Article in Portuguese | LILACS | ID: biblio-996728

ABSTRACT

A coqueluche é uma doença infecciosa aguda, transmissível, com predileção pelo trato respiratório, caracterizada por paroxismos de tosse seca e considerada uma importante causa de morbidade e mortalidade infantil. A resposta imunológica humoral e celular do hospedeiro promove a contenção da infecção, pois essas respostas se caracterizam como importantes linhas de defesa durante a infecção e colonização da bactéria. Dessa forma, esta revisão bibliográfica procurou descrever os mecanismos mais eficazes de resposta imune contra Bordetella pertussis e abordar os mecanismos de evasão utilizados pelo patógeno.


Pertussis is a transmissible infectious disease with a predilection for the respiratory tract characterized by paroxysms of dry cough. It is considered an important cause of child morbidity and mortality. The humoral and cellular immune responses of the host promote the containment of the infection, and these responses are characterized as important lines of defense during infection and colonization of the bacterium. Thus, this literature review sought to describe the most effective immune response mechanisms against Bordetella pertussis and to address the avoidance mechanisms used by the pathogen.


Subject(s)
Humans , Bordetella pertussis , Whooping Cough , Bacteria , Dendritic Cells , Vaccines , Mortality , Cough/diagnosis , Dose-Response Relationship, Immunologic , Immunity, Cellular , Macrophages , Neutrophils , Noxae
12.
Rio de Janeiro; s.n; 2019. xv, 113 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1049507

ABSTRACT

O Toxoplasma gondii é um parasito intracelular obrigatório, capaz de infectar vários tipos de células nucleadas, sendo compartimentalizado no vacúolo parasitóforo. Uma vez no vacúolo, o parasita é capaz de induzir diversas alterações na célula hospedeira que visam sua sobrevivência, dentre elas, a indução da biogênese de corpúsculos lipídicos (CLs). CLs são organelas presentes em todos os tipos celulares, com várias funções como, armazenamento de lipídios, regulação do metabolismo lipídico, tráfego de membranas e controle da síntese e secreção de mediadores inflamatórios. Porém, até o momento, pouco se sabe a respeito da função dos CLs na infecção pelo T. gondii em células humanas. Neste trabalho investigamos a participação dos CLs durante a infecção de células dendríticas humanas (hDC) por T. gondii. Nossos dados mostraram na cinética de infecção em hDC, pico de infecção e replicação em 24 horas (30%), seguidos de queda em 48 horas (10%). A infecção promoveu aumento de CD83 e MHC II na membrana, além da produção de TNF-α, IL-6, IL-8, IP-10 e MIF. A análise da viabilidade do parasita intracelular mostrou que as hDC foram capazes de destruir os parasitos intracelulares (60%). A infecção levou à perda da viabilidade da célula hospedeira em 48 horas de infecção (50%), ao mesmo tempo em que induziu a maior biogênese de CLs nessas células (30CL/cél)


O aumento da taxa de infecção fez com que a biogênese de CLs e a perda da viabilidade das células hospedeiras ocorressem de forma mais precoce, já em 24 horas de infecção. Os tratamentos com o inibidor (C75) da enzima ácido graxo sintase (FAS) ou inibidor (A922500) da enzima diacilglicerol aciltransferase 1 (DGAT1) foram capazes de reduzir a biogênese de CLs (3 CL/cél) e diminuíram também o percentual de células infectadas e a taxa de replicação do parasito, fazendo com que ela ocorresse de forma mais lenta. O mesmo fenômeno pôde ser visto quando as células foram cultivadas em soro fetal bovino delipidado. Além disso, os tratamentos se mostraram protetivos para as células hospedeiras durante a infecção, mantendo sua viabilidade (~80%). O tratamento com o inibidor da DGAT1 ainda reduziu a presença de MHC I na membrana. A suplementação com ácido oleico em células tratadas com o inibdor da DGAT1, recuperou a taxa de infecção e, de forma parcial, auxiliou na replicação do parasita frente à ausência dos CLs. Em conclusão, nossos dados sugerem que os CLs possuem funções tanto como fonte de nutrientes para o T. gondii, quanto na modulação da resposta imune da hDC. (AU)


Subject(s)
Humans , Animals , Toxoplasma , Dendritic Cells , Toxoplasmosis
13.
VozAndes ; 30(2): 43-47, 2019.
Article in Spanish | LILACS | ID: biblio-1050606

ABSTRACT

La Neoplasia de Células Dendríticas Plasmocitoides blásticas (Blastic Plasmacytoid dendritic cell neoplasm ­ BPDCN) es una neoplasia hematológica rara, agresiva, de difícil diagnóstico y con alta mortalidad. Se describe el primer caso en el Ecuador de un paciente joven sin antecedentes patológicos relevantes, ingresado al servicio de Medicina Interna del Hospital Enrique Garcés por presentar máculas cutáneas, artralgias y mialgias, que se complica con derrame pleural tipo exudativo y mala mecánica respiratoria. Exámenes de extensión revelaron: Leucemia mieloide aguda de tipo M2, motivo por el cual fue referido a centro oncológico de referencia para completar estudio y manejo. Estudios citogenéticos y fenotípicos corroboraron el diagnóstico de BPDCN, se instauró tratamiento con protocolo Hyper-CVAD, sin embargo, el paciente presentó compromiso respiratorio, renal y hematológico que progresó a choque refractario y óbito. La naturaleza agresiva de esta rara leucemia es una limitante en el tiempo para instaurar un tratamiento dirigido, determinando en la mayoría de los casos una alta mortalidad


La Neoplasia de Células Dendríticas Plasmocitoides blásticas (Blastic Plasmacytoid dendritic cell neoplasm ­ BPDCN) es una neoplasia hematológica rara, agresiva, de difícil diagnóstico y con alta mortalidad. Se describe el primer caso en el Ecuador de un paciente joven sin antecedentes patológicos relevantes, ingresado al servicio de Medicina Interna del Hospital Enrique Garcés por presentar máculas cutáneas, artralgias y mialgias, que se complica con derrame pleural tipo exudativo y mala mecánica respiratoria. Exámenes de extensión revelaron: Leucemia mieloide aguda de tipo M2, motivo por el cual fue referido a centro oncológico de referencia para completar estudio y manejo. Estudios citogenéticos y fenotípicos corroboraron el diagnóstico de BPDCN, se instauró tratamiento con protocolo Hyper-CVAD, sin embargo, el paciente presentó compromiso respiratorio, renal y hematológico que progresó a choque refractario y óbito. La naturaleza agresiva de esta rara leucemia es una limitante en el tiempo para instaurar un tratamiento dirigido, determinando en la mayoría de los casos una alta mortalidad


Subject(s)
Humans , Male , Female , Bone Marrow/immunology , Leukemia , Dendritic Cells , Leukemia, Myeloid, Acute , Neoplasms
14.
Immune Network ; : e13-2019.
Article in English | WPRIM | ID: wpr-740215

ABSTRACT

6-kDa early secretory antigenic target (ESAT6), a virulent factor of Mycobacterium tuberculosis, is involved in immune regulation. However, the underlying mechanism behind the activation and maturation of dendritic cells (DCs) by ESAT6 remains unclear. In this study, we investigated the effect on TLRs signaling on the regulation of ESAT6-induced activation and maturation of DCs. ESAT6 induced production of IL-6, TNF-α, and IL-12p40 in bone marrow-derived dendritic cells (BMDCs) from wild-type and TLR2-deficient mice, with this induction abolished in TLR4-deficient cells. NF-κB is essential for the ESAT6-induced production of the cytokines in BMDCs. TLR4 was also required for ESAT6-induced activation of NF-κB and MAPKs in BMDCs. ESAT6 additionally upregulated the expression of surface molecules CD80, CD86, and MHC-II, and also promoted the ability of CD4⁺ T cells to secrete IFN-γ via the TLR4-dependent pathway. Our findings suggest that TLR4 is critical in the activation and maturation of DCs in response to ESAT6.


Subject(s)
Animals , Cytokines , Dendritic Cells , Interleukin-12 Subunit p40 , Interleukin-6 , Mice , Mycobacterium tuberculosis , Mycobacterium , T-Lymphocytes , Toll-Like Receptor 4
15.
Immune Network ; : e1-2019.
Article in English | WPRIM | ID: wpr-740213

ABSTRACT

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of anti-microbial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72−/− mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.


Subject(s)
Animals , Antigens, Nuclear , Autoantibodies , Autoantigens , Autoimmune Diseases , Autoimmunity , B-Lymphocytes , Cytoplasm , Dendritic Cells , Discrimination, Psychological , Humans , Immunoreceptor Tyrosine-Based Inhibition Motif , Lectins, C-Type , Lupus Erythematosus, Systemic , Mice , RNA
16.
Immune Network ; : e4-2019.
Article in English | WPRIM | ID: wpr-740210

ABSTRACT

Long noncoding RNAs (lncRNAs) are non-protein coding RNAs of more than 200 nucleotides in length. Despite the term “noncoding”, lncRNAs have been reported to be involved in gene expression. Accumulating evidence suggests that lncRNAs play crucial roles in the regulation of immune system and the development of autoimmunity. lncRNAs are expressed in various immune cells including T lymphocytes, B lymphocytes, macrophages, neutrophils, dendritic cells, and NK cells, and are also involved in the differentiation and activation of these immune cells. Here, we review recent studies on the role of lncRNAs in immune regulation and the differential expression of lncRNAs in various autoimmune diseases.


Subject(s)
Autoimmune Diseases , Autoimmunity , B-Lymphocytes , Clinical Coding , Dendritic Cells , Gene Expression , Immune System , Killer Cells, Natural , Macrophages , Neutrophils , Nucleotides , RNA , RNA, Long Noncoding , T-Lymphocytes
17.
Immune Network ; : e6-2019.
Article in English | WPRIM | ID: wpr-740208

ABSTRACT

Plasmacytoid dendritic cells (pDCs) are a unique subset of cells with different functional characteristics compared to classical dendritic cells. The pDCs are critical for the production of type I IFN in response to microbial and self-nucleic acids. They have an important role for host defense against viral pathogen infections. In addition, pDCs have been well studied as a critical player for breaking tolerance to self-nucleic acids that induce autoimmune disorders such as systemic lupus erythematosus. However, pDCs have an immunoregulatory role in inducing the immune tolerance by generating Tregs and various regulatory mechanisms in mucosal tissues. Here, we summarize the recent studies of pDCs that focused on the functional characteristics of gut pDCs, including interactions with other immune cells in the gut. Furthermore, the dynamic role of gut pDCs will be investigated with respect to disease status including gut infection, inflammatory bowel disease, and cancers.


Subject(s)
Dendritic Cells , Immune Tolerance , Inflammatory Bowel Diseases , Interferon Type I , Lupus Erythematosus, Systemic , Mucous Membrane
18.
Article in English | WPRIM | ID: wpr-739395

ABSTRACT

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.


Subject(s)
Administration, Intranasal , Animals , Anti-Allergic Agents , Calcitriol , Cell Proliferation , Dendritic Cells , Eosinophils , Flow Cytometry , Immunoglobulin E , Immunoglobulin G , Immunoglobulins , Inflammation , Interleukin-10 , Interleukin-13 , Interleukin-4 , Interleukin-5 , Lymph Nodes , Lymphocytes , Major Histocompatibility Complex , Mice , Models, Animal , Ovalbumin , Ovum , Rhinitis, Allergic , RNA, Messenger , Vitamin D
19.
Article in English | WPRIM | ID: wpr-766327

ABSTRACT

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of dendritic cells resulting in local or systemic symptoms. The clinical symptoms of patients with Langerhans cell histiocytosis depend on the site and the degree of involvement. This article describes two case histories of unifocal bony Langerhans cell histiocytosis with mandibular involvement and further discusses the appropriate management of such via a review of the literature.


Subject(s)
Dendritic Cells , Histiocytosis, Langerhans-Cell , Humans , Mandible
20.
Journal of Experimental Hematology ; (6): 1272-1276, 2019.
Article in Chinese | WPRIM | ID: wpr-775729

ABSTRACT

OBJECTIVE@#To explore the method of isolation, purification and differentiation of hematopoietic stem cells (HSCs) into dendritic cells (DC) in lung tissue of mouse, so as to provide theoretical basis and experimental methods for the study of hematopoietic stem cells in mouse lung tissue.@*METHODS@#Lung tissues of 4 male C57 mice were digested, separated and purified into mononuclear cells by type I collagenase, type I DNA enzyme and lymphocyte isolation solution. LinSca-1c-Kit cells, which are hematopoietic stem cells (HSCs) were identified and sorted by flow cytometry. Stem cell factor (SCF) and interleukin 3 (IL-3) were added in the obtained HSCs to promote cell proliferation. After discontinuation of SCF and IL-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 were added to induce differentiation of HSCs into DCs, and lipopolysaccharide (LPS) was added to promote cell maturation. The morphology of DCs was observed under inverted microscope, the expression of CD80, CD86, CD11c and MII-II on the surface of DCs was analyzed by flow cytometry, and the expression level of IL-12 was detected by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#2419.67±247.59 HSCs were collected from lung tissue mononuclear cells of 4 mice identified by flow cytometry with purity: (7.16±0.43)%. HSCs were amplified 62.34±3.23 times by induction with SCF and IL-3 for 7 days. After induction culture for 15 days, mature dendritic cells were obtained with typical dendrites on the cell surface, the DC expressed dendritic cell-specific surface molecules CDllc (92.62±3.68)%,MHC-II (83.89±6.28)%, CD80 (75.96±5.13)%, CD86(72.07±4.38)%, and the expression level of IL-12 was 136.12±16.59 pg/ml detected by ELISA.@*CONCLUSION@#There are HSCs in lung tissue, which can be transformed into DCs by cytokine induction and proliferation.


Subject(s)
Animals , Cell Differentiation , Cells, Cultured , Dendritic Cells , Granulocyte-Macrophage Colony-Stimulating Factor , Hematopoietic Stem Cells , Male , Mice
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