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SOCS3 treatment prevents the development of alopecia areata by inhibiting CD8+ T cell-mediated autoimmune destruction
- Source :
- Oncotarget
- Publication Year :
- 2016
-
Abstract
- // Zhen Gao 1 , Yu-Qing Jin 2 , Wei Wu 1 1 Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 Department of Plastic Surgery, Shanghai International Medical Center, Shanghai, China Correspondence to: Wei Wu, email: babevivi@126.com Keywords: alopecia areata, SOCS3, IFN-γ, autoimmune, hair follicle Received: October 02, 2016 Accepted: February 23, 2017 Published: March 23, 2017 ABSTRACT Alopecia areata is one of the most common autoimmune diseases resulting from T cell-mediated damage of hair follicles. CD8+ T cells infiltrate hair follicles and are responsible for destruction of hair follicles. However the underlying mechanisms for hair loss remain still obscure. In the present study, we identified that suppressor of cytokine signaling-3 (SOCS3), a classical inhibitor of cytokine signaling, significantly inhibits CD8+T cell maturation, interferon-γ (IFN-γ) production and alopecia areata. SOCS3 is downregulated in the skin of alopecia areata patients and murine autoimmune alopecia model. Furthermore, SOCS3 treatment prevents the development of alopecia areata in the graft model. SOCS3 decreases the CD44 high CD62L low effector memory CD8+ T cells, resulting in the decrease of IFN-γ production. The expression of Fas and major histocompatibility complex-1 (MHC I) is upregulated in skin from C3H/HeJ alopecia areata mice, and this increase is suppressed by SOCS3. The SOCS3 level is negative correlation with the Fas and MHC I level in patients with alopecia areata. These results suggest that SOCS3 treatment may be an effective strategy to treat autoimmune alopecia as well as to more generally prevent cytokine-dependent tissue destruction in inflammatory diseases.
- Subjects :
- 0301 basic medicine
Male
Alopecia Areata
medicine.medical_treatment
T cell
Gene Expression
Apoptosis
Autoimmunity
CD8-Positive T-Lymphocytes
Immunophenotyping
03 medical and health sciences
Mice
0302 clinical medicine
T-Lymphocyte Subsets
medicine
Cytotoxic T cell
Animals
Humans
SOCS3
fas Receptor
skin and connective tissue diseases
IFN-γ
integumentary system
hair follicle
business.industry
digestive, oral, and skin physiology
Histocompatibility Antigens Class I
autoimmune
Alopecia areata
medicine.disease
Hair follicle
Recombinant Proteins
Disease Models, Animal
030104 developmental biology
Hair loss
Cytokine
medicine.anatomical_structure
Oncology
Suppressor of Cytokine Signaling 3 Protein
Immunology
Cytokines
business
Immunologic Memory
CD8
Biomarkers
030215 immunology
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....c38fd749a483b07e3cb5f3b3701f2fa2