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1.
Dermatologie (Heidelb) ; 75(6): 459-465, 2024 Jun.
Article in German | MEDLINE | ID: mdl-38780777

ABSTRACT

BACKGROUND: The incidence and severity of alopecia vary mainly depending on the chemotherapeutic agent used or other drug groups. The pathogenetic characteristics of the different forms of alopecia are reflected in the clinical presentation and, in some cases, in the resulting recommendations for prophylaxis. OBJECTIVES: To provide an overview of the pathogenesis, clinical presentation, diagnosis and prophylaxis of alopecia with chemotherapeutic agents, hedgehog inhibitors, targeted therapies and immune checkpoint inhibitors. MATERIALS AND METHODS: Based on the current S3 guideline "Supportive therapy", an extensive literature search was carried out. RESULTS AND CONCLUSION: Chemotherapy-induced hair loss (CIA) occurs in up to 65% of cases. Anagen effluvium is observed as early as 1-3 weeks after the start of treatment and is reversible in most cases. Alopecia associated with inhibitors of the Sonic Hedgehog signaling pathway (HHIA) such as vismodegib or sonidegib are observed in up to 60% of cases. They are characterized by telogen effluvium. BRAF or immune checkpoint inhibitors lead significantly less frequently to alopecia (BRAFA, CPIA). According to taxane-based chemotherapy protocols, scalp cooling can help to prevent higher-grade CIA. If CIA or other forms of alopecia are expected, early contact with self-help organizations and early prescriptions for wigs should be offered.


Subject(s)
Alopecia , Antineoplastic Agents , Hedgehog Proteins , Immune Checkpoint Inhibitors , Humans , Alopecia/chemically induced , Alopecia/prevention & control , Alopecia/immunology , Alopecia/pathology , Hedgehog Proteins/antagonists & inhibitors , Hedgehog Proteins/metabolism , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Molecular Targeted Therapy/adverse effects
2.
J Cell Physiol ; 239(4): e31181, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38219076

ABSTRACT

Stress-induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress-induced hair loss was related to an imbalanced immune microenvironment. Screening the skin-infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress-induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress-induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in-vivo and in-vitro studies confirm that NE can induce macrophage polarization toward M1 through the ß-adrenergic receptor, Adrb2. Transcriptome, enzyme-linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase-1 inflammasome signaling and its downstream effector interleukin 18 (IL-18) and interleukin 1 beta (IL-1ß) were significantly upregulated in the NE-treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase-1, IL-18, and IL-1ß. Indeed, IL-18 and IL-1ß treatments lead to apoptosis of HFSCs. More importantly, blocking IL-18 and IL-1ß signals reversed HFSCs depletion in skin organoid models and attenuated stress-induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)-endocrine (NE)-immune (M1 macrophages) axis in stress-induced hair shedding and suggestes that IL-18 or IL-1ß may be promising therapeutic targets.


Subject(s)
Alopecia , Interleukin-18 , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein , Stress, Psychological , Animals , Mice , Alopecia/immunology , Caspases , Inflammasomes , Interleukin-18/genetics , Interleukin-18/pharmacology , Interleukin-18/therapeutic use , Interleukin-1beta/genetics , Interleukin-1beta/pharmacology , Interleukin-1beta/therapeutic use , Macrophages , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Stress, Psychological/complications , Norepinephrine/therapeutic use , Adrenergic alpha-2 Receptor Agonists/therapeutic use , Apoptosis/drug effects
3.
J Immunol Res ; 2022: 7471246, 2022.
Article in English | MEDLINE | ID: mdl-35155688

ABSTRACT

BACKGROUND: Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth in vitro and in vivo for potentially treating immune-mediated alopecia and further exploring the underlying mechanism. METHODS: Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established in vivo; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real-time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq). RESULTS: ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF-α signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/ß-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice. CONCLUSION: ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/ß-catenin signaling pathway, and the TNF-α signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.


Subject(s)
Adipose Tissue/pathology , Alopecia/metabolism , Exosomes/metabolism , Hair/physiology , Mesenchymal Stem Cells/metabolism , Alopecia/immunology , Animals , Biological Therapy , Cells, Cultured , Disease Models, Animal , Humans , Male , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Rats , Rats, Sprague-Dawley , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Wnt Signaling Pathway
4.
Pharmacol Rep ; 74(1): 216-228, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34897595

ABSTRACT

BACKGROUND: Early-onset androgenic alopecia is considered the phenotypic equivalent of polycystic ovary syndrome in men. The purpose of the current study was to investigate whether the presence of early-onset male-pattern baldness modulates metabolic effects of metformin. METHODS: This prospective case-control study included 2 groups of men at high risk for type 2 diabetes: 72 individuals with androgenic alopecia (group A) and 75 subjects with normal hair growth (group B). Both groups were matched for age, blood pressure, body mass index, insulin sensitivity and plasma lipids. Glycated hemoglobin, glucose, plasma lipids, indices of insulin sensitivity/resistance, sex hormones, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D were determined before and after metformin treatment (1.7 g daily). RESULTS: Twelve-month metformin treatment reduced fat content, waist circumference, glycated hemoglobin, glucose and triglycerides, as well as improved insulin sensitivity. Although observed in both study populations, these effects were more pronounced in group B. Moreover, metformin decreased hsCRP and bioavailable testosterone levels in group B, as well as reduced 25-hydroxyvitamin D concentration in group A. Treatment-induced changes in glucose homeostasis markers correlated with the impact of metformin on hsCRP and 25-hydroxyvitamin D levels. CONCLUSIONS: Metabolic effects of metformin in males are attenuated if they have coexisting early-onset androgenic alopecia. This finding may be partially explained by differences in severity of low-grade systemic inflammation and vitamin D status. The obtained results, requiring confirmation in large prospective studies, suggest that men with early-onset male-pattern baldness benefit to a lesser degree from metformin treatment than other men at high risk for type 2 diabetes.


Subject(s)
Alopecia , Diabetes Mellitus, Type 2 , Drug Monitoring/methods , Inflammation/metabolism , Metformin , Vitamin D/blood , Alopecia/complications , Alopecia/immunology , Alopecia/metabolism , Biological Availability , Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Insulin Resistance , Male , Metformin/administration & dosage , Metformin/pharmacokinetics , Middle Aged , Patient Selection , Testosterone/blood , Treatment Outcome
5.
Immunity ; 54(10): 2321-2337.e10, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34582748

ABSTRACT

Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here we found that transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating the skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired the innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-, and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting ß-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation.


Subject(s)
ADAM10 Protein/immunology , Amyloid Precursor Protein Secretases/immunology , Dysbiosis/immunology , Hair Follicle/pathology , Lymphocytes/immunology , Membrane Proteins/immunology , Receptors, Notch/immunology , Skin/microbiology , Alopecia/immunology , Alopecia/pathology , Animals , Corynebacterium , Dysbiosis/pathology , Female , Hair Follicle/immunology , Immunity, Innate , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Mice , Signal Transduction/immunology , Skin/immunology , Skin/pathology
6.
J Dermatol Sci ; 103(1): 33-40, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34158211

ABSTRACT

BACKGROUND: Hair follicle undergoes a growth cycle under the regulation of dermal papilla cells. Due to their enormous roles, these fibroblast cells have been used in various in vitro studies as a screening model to evaluate the effect of hair growth regulating agents. OBJECTIVE: In the current study, we aim to check the hair growth potential effect of Argan press cake (APC) extracted using 50 or 80 % aqueous ethanol on human hair follicle dermal papilla cells (HFDPCs) and to determine the molecular mechanism. METHODS: APC were applied to HFDPCs, then cell proliferation assays, mitochondrial biogenesis assay, and oxidative stress assay were assessed. DNA microarray was performed from the cells treated with our samples and minoxidil. Validation of the results was done using Quantitative Real-Time PCR with primers for hair-growth related genes. GC/MS analysis was used to determine the compounds contained in APC 50 and 80 %. RESULTS: APC enhanced cell proliferation along with the stimulation of the ATP content. Additionally, APC had an anti-oxidant activity against H2O2 mediated oxidative stress preventing dermal papilla cell senescence. Consistent with this, global gene profiling analysis showed an activation of hair growth-related pathway, and a downregulation of inflammation- and oxidative stress-related genes by APC extracts. GC/MS analysis revealed that these extracts contained pure fatty acids, derived sugar chains, and pure compounds including tocopherols, squalene, and spinasterol. CONCLUSION: Taken together, here we showed that APC extracts had an effect on stimulating hair growth while inhibiting the inflammation and the oxidative stress of HFDPCs and thus can potentially contribute to an anti-hair loss drug development.


Subject(s)
Alopecia/drug therapy , Hair Follicle/drug effects , Plant Extracts/pharmacology , Sapotaceae/chemistry , Alopecia/immunology , Antioxidants , Cell Line , Cell Proliferation/drug effects , Cells, Cultured , Drug Evaluation, Preclinical , Hair Follicle/immunology , Humans , Oxidative Stress/drug effects , Oxidative Stress/immunology , Plant Extracts/therapeutic use
7.
Clin Exp Dermatol ; 46(7): 1248-1254, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33837578

ABSTRACT

BACKGROUND: Facial papules (FPs) are considered to be created by the inflammatory process, which involves facial vellus hairs, in frontal fibrosing alopecia. AIM: To demonstrate the histopathological features of FPs and the composition of the inflammatory infiltrate. METHODS: In total, 18 patients with FPs were enrolled in the study after histopathological confirmation of lichen planopilaris. Histopathological evaluation of the specimens was performed by two dermatopathologists. The samples were immunostained with CD4, CD8 and CD123 monoclonal antibodies, and the percentage and proportion of cells stained with these markers were investigated. RESULTS: A follicular lichenoid reaction and perifollicular fibrosis were present in all cases. Vellus hairs were detected in 83.3% of biopsy specimens (15 cases), all of which were involved by the inflammation. The majority of the follicles (72%) revealed follicular plugs. Reduction and destruction of elastic fibres were visible in the perifollicular (adventitial) and the papillary dermis (100% and 78% of specimens, respectively). Prominent sebaceous glands and dilated ducts were detected in 78% and 72% of samples, respectively. CD4-positive T cells formed 67.72% and CD8-positive T cells 32.28% of the infiltrate, and the mean CD4/CD8 ratio was 2.48. In 13 (72.2%) biopsy specimens < 10% of the infiltrate was positive for CD123 marker. CONCLUSIONS: Perifollicular inflammation, fibrosis and elastic-fibre destruction were constant histopathological features of FPs; furthermore, prominent sebaceous glands were present in the majority of samples. We also observed a CD4-positive predominance in the infiltrate.


Subject(s)
Alopecia/pathology , Face/pathology , Facial Dermatoses/pathology , Lichen Planus/pathology , Adult , Aged , Alopecia/immunology , CD4 Antigens/analysis , Facial Dermatoses/immunology , Female , Humans , Immunohistochemistry , Lichen Planus/immunology , Male , Middle Aged , T-Lymphocytes/immunology
9.
Exp Dermatol ; 30(5): 723-732, 2021 05.
Article in English | MEDLINE | ID: mdl-33523560

ABSTRACT

Alopecia areata (AA) is a multi-factors disease characterized by non-scarring hair loss. AA could be classified into three main clinical phenotypes including patchy type AA (AAP), alopecia totalis (AT) and alopecia universalis (AU) based on the severity and areas of hair loss. Recent studies suggested immunological factor was critical in AA, but the precise aetiology and pathogenesis of AA still need exploration. In the work, we screened two gene expression profiles (GSE45512 and GSE68801) from Gene Expression Omnibus (GEO). Based on the two data sets, 10 upregulated genes and 107 downregulated genes in AA skin biopsies were identified. CCL13, as one of the remarkably upregulated genes, was found to have potential biological functions in aberrant immune response of AA according to the GO and KEGG analyses. The PPI network showed CCL13 was associated with multiple immune-related genes. The expression of CCL13 was increased depending on the severity of disease in AA patients. Cytotoxic lymphocytes, T cells and myeloid dendritic cells accumulated remarkably in scalp tissue depending on the severity of AA, and CCL13 was significantly correlated to cytotoxic lymphocytes, T cells and myeloid dendritic cells in AA patients. Our RT-PCR and ELISA results found CCL13 was upregulated in skin biopsy and serum of AA patients, and the immunohistochemistry (IHC) detection showed CCL13 was expressed by both the hair follicle epithelium and infiltrating immune cells. In conclusion, the upregulated of CCL13 and subsequent immune cell infiltration was related to AA, which could be a promising target for diagnosis and therapy in AA patients.


Subject(s)
Alopecia Areata/immunology , Alopecia/immunology , Monocyte Chemoattractant Proteins/immunology , Alopecia/pathology , Alopecia Areata/pathology , Autoimmunity , Disease Progression , Hair Follicle/immunology , Histocytochemistry , Humans
10.
Lupus ; 30(5): 785-794, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33554715

ABSTRACT

BACKGROUND: Age at disease onset may modulate systemic lupus erythematosus (SLE), but its relation to cutaneous/extracutaneous manifestation remains understudied. OBJECTIVE: To compare the cutaneous, systemic features, laboratory characteristics, and disease severity between late- and adult-onset SLE patients. METHODS: Analyses of the cutaneous, systemic involvement, laboratory investigations, SLE disease activity index 2000 (SLEDAI-2K), and disease damage were performed to compare between groups. RESULTS: Of 1006 SLE patients, 740 and 226 had adult- (15-50 years) and late-onset (>50 years), respectively. Among 782 with cutaneous lupus erythematosus (CLE), acute CLE (ACLE) and chronic CLE (CCLE) were more common in the adult- and late-onset SLE, respectively (p = 0.001). Multivariable logistic regression analysis demonstrated that male patients and skin signs, including papulosquamous subacute CLE, discoid lupus erythematosus, and lupus profundus, were associated with late-onset SLE (all p < 0.05). Late-onset SLE had lower lupus-associated autoantibodies, and systemic involvement (all p < 0.05). ACLE, CCLE, mucosal lupus, alopecia, and non-specific lupus were related to higher disease activity in adult-onset SLE (all p < 0.001). There was no difference in the damage index between the two groups. CONCLUSIONS: Late-onset SLE had a distinct disease expression with male predominance, milder disease activity, and lower systemic involvement. Cutaneous manifestations may hold prognostic values for SLE.


Subject(s)
Lupus Erythematosus, Cutaneous/immunology , Lupus Erythematosus, Cutaneous/pathology , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Acute Disease , Adult , Age of Onset , Aged , Alopecia/diagnosis , Alopecia/etiology , Alopecia/immunology , Autoantibodies/blood , Clinical Laboratory Techniques/statistics & numerical data , Clinical Laboratory Techniques/trends , Cross-Sectional Studies , Female , Humans , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Discoid/diagnosis , Lupus Erythematosus, Systemic/diagnosis , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index , Sex Factors , Thailand/epidemiology
11.
Arch Dermatol Res ; 313(9): 751-758, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33399960

ABSTRACT

Programmed cell death protein-1 (PD-1) is primarily recognized as an inhibitory receptor involved in the regulation of immunological tolerance. However, recent studies have indicated that PD-1/PD-L1 signaling could also regulate the functions of nonimmune cells and may be involved in regulating hair biology. In this study, we showed in a mouse model of depilation-induced hair cycling that PD-1/PD-L1 are expressed in the murine epidermis and hair follicle (HF) in a hair cycle-dependent manner. During HF morphogenesis, PD-1 expression was strongly decreased during the anagen phase compared with the catagen and telogen phases. PD-L1 expression was enhanced during the catagen phase compared with the anagen and telogen phases. Moreover, direct blockade of PD-L1 not only accelerated hair anagen phase onset but also delayed catagen progression. In conclusion, our findings indicated that PD-1/PD-L1 signaling may act as a negative regulator of hair cycle transition. Anti-PD-1/PD-L1 therapy may thus be a promising strategy for treating anagen-reduced hair loss.


Subject(s)
B7-H1 Antigen/metabolism , Hair Follicle/growth & development , Programmed Cell Death 1 Receptor/metabolism , Alopecia/drug therapy , Alopecia/immunology , Animals , Female , Hair Follicle/drug effects , Hair Follicle/immunology , Hair Follicle/metabolism , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Immune Tolerance/drug effects , Mice , Models, Animal , Morphogenesis/drug effects , Morphogenesis/immunology , Signal Transduction/drug effects , Signal Transduction/immunology
14.
Transplant Proc ; 53(1): 228-232, 2021.
Article in English | MEDLINE | ID: mdl-32605770

ABSTRACT

INTRODUCTION: Alopecia is a common complication in patients following kidney transplantation; however, reports regarding liver transplantation patients are still few. METHODS: This study followed 111 children who underwent living related liver transplantation. Alopecia patients and its possible risk factors were analyzed. RESULTS: Alopecia occurred in 3 patients (2.7%). Underlying diseases were biliary atresia and Alagille syndrome. Clinically significant alopecia (universal alopecia) occurred in 1 patient with Alagille syndrome. All patients received tacrolimus as their immunosuppression drug. None of the patients who received cyclosporine experienced alopecia. The onset of alopecia ranged from 7 to 28 months after transplantation. Alopecia was treated with a topical corticosteroid and topical tacrolimus, but 1 patient with clinically severe alopecia required conversion from tacrolimus to cyclosporine A. CONCLUSIONS: Alopecia is 1 complication seen in children receiving tacrolimus therapy following living donor liver transplant. Prompt management of this cosmetic complication should be done to ensure patients' compliance to medication regimen.


Subject(s)
Alopecia/immunology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Liver Transplantation , Tacrolimus/adverse effects , Alopecia/epidemiology , Child, Preschool , Cyclosporine/therapeutic use , Female , Humans , Immunosuppression Therapy/adverse effects , Infant , Liver Transplantation/adverse effects , Living Donors , Male
15.
Stem Cell Rev Rep ; 16(6): 1105-1120, 2020 12.
Article in English | MEDLINE | ID: mdl-32789558

ABSTRACT

The Primary Scarring Alopecias are characterised by the irreversible destruction and fibrosis of hair follicles, leading to permanent and often disfiguring loss of hair. The pathophysiology of these diseases is not well understood. However, follicular-fibrosis and loss of the stem-cell niche appears to be a common theme. This review explores the pathogenesis of primary scarring alopecias, asking what happens to the stem cells of the hair follicle and how they may contribute to the progression of these diseases. Bulge-resident cells are lost (leading to loss of capacity for hair growth) from the follicle either by inflammatory-mediate apoptosis or through epigenetic reprogramming to assume a mesenchymal-like identity. What proportion of bulge cells is lost to which process is unknown and probably differs depending on the individual PCA and its specific inflammatory cell infiltrate. The formation of fibroblast-like cells from follicular stem cells may also mean that the cells of the bulge have a direct role in the pathogenesis. The identification of specific cells involved in the pathogenesis of these diseases could provide unique diagnostic and therapeutic opportunities to prevent disease progression by preventing EMT and specific pro-fibrotic signals.


Subject(s)
Alopecia/pathology , Alopecia/therapy , Cicatrix/pathology , Cicatrix/therapy , Stem Cell Niche , Alopecia/immunology , Animals , Biomarkers/metabolism , Cicatrix/immunology , Fibrosis , Hair Follicle/growth & development , Hair Follicle/pathology , Humans
17.
J Invest Dermatol ; 140(8): 1576-1588, 2020 08.
Article in English | MEDLINE | ID: mdl-31972250

ABSTRACT

Nuclear inhibitor of protein phosphatase 1 (NIPP1) is a ubiquitously expressed nuclear protein that regulates functions of protein serine/threonine phosphatase-1 in cell proliferation and lineage specification. The role of NIPP1 in tissue homeostasis is not fully understood. This study shows that the selective deletion of NIPP1 in mouse epidermis resulted in epidermal hyperproliferation, a reduced adherence of basal keratinocytes, and a gradual decrease in the stemness of hair follicle stem cells, culminating in hair loss. This complex phenotype was associated with chronic sterile skin inflammation and could be partially rescued by dexamethasone treatment. NIPP1-deficient keratinocytes massively expressed proinflammatory chemokines and immunomodulatory proteins in a cell-autonomous manner. Chemokines subsequently induced the recruitment and activation of immune cells, in particular conventional dendritic cells and Langerhans cells, accounting for the chronic inflammation phenotype. The data identifies NIPP1 as a key regulator of epidermal homeostasis and as a potential target for the treatment of inflammatory skin diseases.


Subject(s)
Alopecia/immunology , Chemokines/metabolism , Dermatitis/immunology , Epidermis/pathology , Intracellular Signaling Peptides and Proteins/metabolism , Alopecia/genetics , Alopecia/pathology , Animals , Cell Adhesion/immunology , Cell Proliferation/genetics , Chemokines/immunology , Dermatitis/genetics , Dermatitis/pathology , Disease Models, Animal , Epidermis/immunology , Hair Follicle/immunology , Hair Follicle/pathology , Humans , Intracellular Signaling Peptides and Proteins/genetics , Keratinocytes/immunology , Keratinocytes/pathology , Mice , Mice, Knockout
19.
Exp Dermatol ; 29(3): 322-333, 2020 03.
Article in English | MEDLINE | ID: mdl-31903650

ABSTRACT

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.


Subject(s)
Hair/immunology , Hair/physiology , Immune System/physiology , Alopecia/immunology , Alopecia/physiopathology , Alopecia Areata/immunology , Alopecia Areata/physiopathology , Animals , Biopsy , Cell Cycle , Epithelial-Mesenchymal Transition , Hair Follicle/cytology , Homeostasis , Humans , Mice , Skin/immunology , Skin Physiological Phenomena
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