083 More Expression of IL-17 than IFN-γ from CD49a-negative Tissue-Resident Memory T (Trm) cells at the Hair Bulge and Hair Bulb Region in the Scalp of Chronic Alopecia Areata Patients according to the Foxp3+mTregs depletion

Alopecia areata (AA) and vitiligo are both common skin diseases of autoimmune origin. Both alopecia areata and vitiligo have shown to be affected by oxidative stress. The present work is aimed at evaluating and comparing the serum proinflammatory cytokine levels in AA and nonsegmental vitiligo (NSV). A cross-sectional study was conducted of 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of interferon γ (IFN-γ), interleukin- (IL-) 1β, and IL-6 were determined quantitatively by ELISA method. Our analysis identified a signature of oxidative stress associated with AA and NSV, characterized by elevated levels of IFN-γ (AA: p=0.007283; NSV: p=0.038467), IL-1β (AA; NSV: p≤0.001), and IL-6 (AA; NSV: p≤0.001). IL-6 was also significantly increased in NSV patients in comparison with AA patients (p=0.004485). Our results supported the hypothesis that oxidative stress may play a significant role in promoting and amplifying the inflammatory process both in AA and vitiligo. The complex understanding of both disease etiopathogenesis involves interrelationships between oxidative stress and autoimmunity. The clinical study registration number is RNN/266/16/KE.

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The Role of Serum Th1, Th2, and Th17 Cytokines in Patients with Alopecia Areata: Clinical Implications

Cells ◽

10.3390/cells10123397 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3397

Author(s):

Anna Waśkiel-Burnat ◽

Marta Osińska ◽

Anna Salińska ◽

Leszek Blicharz ◽

Mohamad Goldust ◽

...

Keyword(s):

Serum Level ◽

Alopecia Areata ◽

Prognostic Markers ◽

Clinical Manifestations ◽

Serum Levels ◽

Th17 Cytokines ◽

Ifn Γ ◽

Pre Treatment ◽

Positive Correlations

Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-β) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy.

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Hair follicle-derived mesenchymal stem cells decrease alopecia areata mouse hair loss and reduce inflammation around the hair follicle

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02614-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Weiyue Deng ◽

Yuying Zhang ◽

Wei Wang ◽

Aishi Song ◽

Omar Mukama ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Hair Follicle ◽

Hair Loss ◽

Alopecia Areata ◽

In Vitro Model ◽

Ifn Γ ◽

Vitro Model

Abstract Background Alopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases. Methods Hair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model. Results AA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 106 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo. Conclusions This study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.

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Epigallocatechin-3 Gallate Inhibits STAT-1/JAK2/IRF-1/HLA-DR/HLA-B and Reduces CD8 MKG2D Lymphocytes of Alopecia Areata Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15122882 ◽

2018 ◽

Vol 15 (12) ◽

pp. 2882

Author(s):

Fatma Hamed ◽

Andrew McDonagh ◽

Sarah Almaghrabi ◽

Youssef Bakri ◽

Andrew Messenger ◽

...

Keyword(s):

Alopecia Areata ◽

Mononuclear Cells ◽

Ex Vivo ◽

Active Agent ◽

Janus Kinase ◽

Jurkat Cells ◽

Cd8 Cells ◽

Hla Dr ◽

Ifn Γ

Background: Alopecia areata (AA) is associated with Interferon- γ (IFN-γ) mediated T-lymphocyte dysfunction and increased circulating Interleukine-17 (IL-17) levels. Epigallocatechin-3-gallate (EGCG) specifically inhibits IFN-γ pathways and unlike Janus Kinase 1 and 2 (JAK1/JAK2) inhibitors (tofacitinib, ruxolitinib), EGCG is safer, more cost-effective, and is a topically active agent. Our objective is to test the mode of action of EGCG in vitro and ex vivo using HaCat, Jurkat cell lines, and peripheral blood mononuclear cells (PBMCs) of AA patients and healthy controls (HCs), respectively. Methods: distribution of T helper cells (Th1, Th17), and cytotoxic cells (CD8) in PBMCs isolated from 30 AA patients and 30 HCs was investigated by flowcytomterty. In vitro treatment of HaCat and Jurkat cells with 40 μm EGCG for 48 h was performed to measure the level of phosphorylation of signal transducer and activator of transcription protein STAT1, and replicated in ex vivo model using PBMCs of AA patients. Results: Interestingly, 40 μm EGCG is capable of completely inhibiting phosphorylation of STAT1 after 48 h in HaCat and Jurkat cells and ex vivo in PBMCs of AA patients. Based on QPCR data, the action of EGCG on p-STAT1 seems to be mediated via downregulation of the expression of JAK2 but not JAK1 leading to the inhibition of human leukocyte antigens (HLA-DR and HLA-B) expression probably via IRF-1. On the other hand, AA patients have significantly increased levels of Th1, Th17, and CD8 cells and the production of IFN-γ and IL-17 by PBMCs in AA patients was significantly higher compared to HC; p = 0.008 and p = 0.006, respectively. Total numbers of CD8+ cells were not significantly different between treated and untreated samples. However, CD8+ cells with positive Natural killer group 2 member D (NKG2D) transmembrane receptor (CD8+ NKG2D+ subset) was significantly reduced when PBMCs were treated with 20 μm EGCG for 48 h. Conclusion: These results suggest that EGCG has a synergistic action that inhibits expression of HLA-DR and HLA-B molecules via the IFN-γ pathway to maintain immune privilege in HF; also it reduces CD8+ NKG2D+ subset.

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The Functional Relevance of the Type 1 Cytokines IFN-γ and IL-2 in Alopecia Areata of C3H/HeJ Mice

Journal of Investigative Dermatology Symposium Proceedings ◽

10.1111/j.0022-202x.2005.10130_5.x ◽

2005 ◽

Vol 10 (3) ◽

pp. 282-283 ◽

Cited By ~ 15

Author(s):

P. Freyschmidt-Paul ◽

M. Zöller ◽

K.J. Mcelwee ◽

J. Sundberg ◽

R. Happle ◽

...

Keyword(s):

Alopecia Areata ◽

Ifn Γ ◽

Functional Relevance

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Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata

International Journal of Molecular Sciences ◽

10.3390/ijms22052618 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2618

Author(s):

Reiko Kageyama ◽

Taisuke Ito ◽

Shiho Hanai ◽

Naomi Morishita ◽

Shinsuke Nakazawa ◽

...

Keyword(s):

Atopic Dermatitis ◽

Alopecia Areata ◽

Inflammatory Disease ◽

Chemokine Receptors ◽

Autoimmune Disorder ◽

Healthy Controls ◽

Remarkable Change ◽

Immunological Properties ◽

Ifn Γ

Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells and CD4+IFN-γ+ cells to CD4+IL-13+ cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8+IFN-γ+ cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4+ cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3+ cells had no remarkable change while the number of CCR4+ cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.

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Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

Cell Transplantation ◽

10.1177/0963689718773311 ◽

2018 ◽

Vol 27 (6) ◽

pp. 994-1004 ◽

Cited By ~ 9

Author(s):

Reza B Jalili ◽

Ruhangiz T Kilani ◽

Yunyuan Li ◽

Mohsen Khosravi-maharlooie ◽

Layla Nabai ◽

...

Keyword(s):

T Cells ◽

Hair Loss ◽

Alopecia Areata ◽

Fibroblast Cell ◽

Hair Follicles ◽

Dermal Fibroblasts ◽

Cell Based Therapy ◽

Tnf Α ◽

Ifn Γ ◽

Draining Lymph Nodes

Alopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.

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