Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Immunol ; 13: 1054260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518752

RESUMO

Herpes stromal keratitis (HSK) is a blinding corneal disease caused by herpes simplex virus-1 (HSV-1), a common pathogen infecting most of the world's population. Inflammation in HSK is chemokine-dependent, particularly CXCL10 and less so the CC chemokines. The atypical chemokine receptor-2 (ACKR2) is a decoy receptor predominantly for pro-inflammatory CC chemokines, which regulates the inflammatory response by scavenging inflammatory chemokines thereby modulating leukocyte infiltration. Deletion of ACKR2 exacerbates and delays the resolution of the inflammatory response in most models. ACKR2 also regulates lymphangiogenesis and mammary duct development through the recruitment of tissue-remodeling macrophages. Here, we demonstrate a dose-dependent upregulation of ACKR2 during corneal HSV-1 infection. At an HSV inoculum dose of 5.4 x 105 pfu, but not at higher dose, ACKR2 deficient mice showed prolonged clinical signs of HSK, increased infiltration of leukocytes and persistent corneal neovascularization. Viral clearance and T cell activation were similar in ACKR2-/- and wild type mice, despite a transient diminished expression of CD40 and CD86 in dendritic cells. The data suggest that ACKR2 fine-tunes the inflammatory response and the level of neovascularization in the HSK.


Assuntos
Ceratite Herpética , Receptores de Quimiocinas , Animais , Camundongos , Quimiocina CXCL10 , Quimiocinas CC , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Receptores de Quimiocinas/metabolismo , Ceratite Herpética/imunologia , Neovascularização da Córnea/imunologia , Neovascularização da Córnea/virologia
2.
Elife ; 112022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35699420

RESUMO

Inflammatory chemokines and their receptors are central to the development of inflammatory/immune pathologies. The apparent complexity of this system, coupled with lack of appropriate in vivo models, has limited our understanding of how chemokines orchestrate inflammatory responses and has hampered attempts at targeting this system in inflammatory disease. Novel approaches are therefore needed to provide crucial biological, and therapeutic, insights into the chemokine-chemokine receptor family. Here, we report the generation of transgenic multi-chemokine receptor reporter mice in which spectrally distinct fluorescent reporters mark expression of CCRs 1, 2, 3, and 5, key receptors for myeloid cell recruitment in inflammation. Analysis of these animals has allowed us to define, for the first time, individual and combinatorial receptor expression patterns on myeloid cells in resting and inflamed conditions. Our results demonstrate that chemokine receptor expression is highly specific, and more selective than previously anticipated.


Assuntos
Quimiocinas , Inflamação , Animais , Proteínas de Transporte , Quimiocinas/genética , Quimiocinas/metabolismo , Expressão Gênica , Inflamação/patologia , Camundongos
3.
Immunity ; 50(2): 378-389.e5, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30784579

RESUMO

Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. In contrast, analysis of cellular recruitment to inflamed sites provides evidence of specificity of receptor use for distinct leukocyte subtypes and no indication of comprehensive redundancy. We find no evidence of involvement of any of these receptors in the recruitment of neutrophils or lymphocytes to resting or acutely inflamed tissues. Our data shed important light on combinatorial inflammatory chemokine receptor function and highlight Ccr2 as the primary driver of myelomonocytic cell recruitment in acutely inflamed contexts.


Assuntos
Eosinófilos/imunologia , Inflamação/imunologia , Monócitos/imunologia , Receptores CCR/imunologia , Animais , Quimiocinas/imunologia , Quimiocinas/metabolismo , Eosinófilos/metabolismo , Perfilação da Expressão Gênica/métodos , Inflamação/genética , Inflamação/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Receptores CCR/genética , Receptores CCR/metabolismo , Receptores CCR1/imunologia , Receptores CCR1/metabolismo , Receptores CCR2/imunologia , Receptores CCR2/metabolismo , Receptores CCR3/imunologia , Receptores CCR3/metabolismo , Receptores CCR5/imunologia , Receptores CCR5/metabolismo
4.
J Leukoc Biol ; 105(3): 497-506, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30517976

RESUMO

Chemokines are members of a large family of chemotactic cytokines that signal through their receptors to mediate leukocyte recruitment during inflammation and homeostasis. The chemokine receptor CXCR2 has largely been associated with neutrophil recruitment. However, there is emerging evidence of roles for chemokines and their receptors in processes other than leukocyte migration. We have previously demonstrated that CXCR2 knockout (KO) mice have thinner skin compared to wild-type mice. Herein we demonstrate that this is due to a thinner subcutaneous adipose layer, as a result of fewer and smaller individual adipocytes. We observe a similar phenotype in other fat depots and present data that suggests this may be due to reduced expression of adipogenesis related genes associated with adipocyte specific CXCR2 signaling. Interestingly, this phenotype is evident in female, but not male, CXCR2 KO mice. These findings expand our understanding of nonleukocyte related chemokine receptor functions and help to explain some previously observed adipose-related phenotypes in CXCR2 KO mice.


Assuntos
Adipócitos/citologia , Adipócitos/metabolismo , Receptores de Interleucina-8B/metabolismo , Células 3T3-L1 , Adipogenia/genética , Animais , Diferenciação Celular/genética , Tamanho Celular , Regulação para Baixo/genética , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/citologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-8B/antagonistas & inibidores , Gordura Subcutânea/anatomia & histologia , Gordura Subcutânea/citologia
6.
Sci Rep ; 7: 42681, 2017 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-28205614

RESUMO

CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...