Resident human dermal γ6T-cells operate as stress-sentinels: Lessons from the hair follicle

被引:21
作者
Uchida, Youhei [1 ]
Gherardini, Jennifer [2 ,3 ]
Pappelbaum, Karin [2 ]
Cheret, Jeremy [3 ]
Schulte-Mecklenbeck, Andreas [4 ]
Gross, Catharina C. [4 ]
Strbo, Natasa [5 ]
Gilhar, Amos [6 ]
Rossi, Alfredo [7 ]
Funk, Wolfgang [8 ]
Kanekura, Takuro [1 ]
Almeida, Luis [2 ]
Bertolini, Marta [2 ]
Paus, Ralf [2 ,3 ,9 ,10 ]
机构
[1] Kagoshima Univ, Dept Dermatol, Grad Sch Med & Dent Sci, Kagoshima, Japan
[2] Monasterium Lab, Munster, Germany
[3] Univ Miami, Dr Phillip Frost Dept Dermatol & Cutaneous Surg, Miller Sch Med, 1600 NW 10th Ave,RMSB 2023A, Miami, FL 33136 USA
[4] Univ Hosp Munster, Dept Neurol, Inst Translat Neurol, Munster, Germany
[5] Univ Miami, Dept Microbiol & Immunol, Miller Sch Med, Miami, FL 33136 USA
[6] Technion Israel Inst Technol, Skin Res Lab, Haifa, Israel
[7] Univ Roma La Sapienza, Dept Clin Internal Anesthesiol & Cardiovasc Sci, Rome, Italy
[8] Dr Dr Med Funk, Clin Plast Aesthet & Reconstruct Surg, Munich, Germany
[9] Univ Manchester, Ctr Dermatol Res, MAHSC, Manchester, Lancs, England
[10] Manchester NIHR Biomed Res Ctr, Manchester, Lancs, England
关键词
Gamma delta T-cells; Hair follicle; Alopecia areata; Stress; Autoimmunity; MICA; NKG2D; ex vivo model; DELTA T-CELLS; GAMMA-DELTA; ALOPECIA-AREATA; IMMUNE PRIVILEGE; CLASS-I; EX-VIVO; SCALP SKIN; RECEPTOR; RECOGNITION; ACTIVATION;
D O I
10.1016/j.jaut.2021.102711
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Murine gamma 6T-cells have stress-surveillance functions and are implicated in autoimmunity. Yet, whether human gamma 6T-cells are also stress sentinels and directly promote autoimmune responses in the skin is unknown. Using a novel (mini-)organ assay, we tested if human dermis resident gamma 6T-cells can recognize stressed human scalp hair follicles (HFs) to promote an alopecia areata (AA)-like autoimmune response. Accordingly, we show that gamma 6Tcells from healthy human scalp skin are activated (CD69+), up-regulate the expression of NKG2D and IFN-gamma, and become cytotoxic when co-cultured with autologous stressed HFs ex vivo. These autologous gamma 6T-cells induce HF immune privilege collapse, dystrophy, and premature catagen, i.e. three hallmarks of the human autoimmune HF disorder, AA. This is mediated by CXCL12, MICA, and in part by IFN-gamma and CD1d. In conclusion, human dermal gamma 6T-cells exert physiological stress-sentinel functions in human skin, where their excessive activity can promote autoimmunity towards stressed HFs that overexpress CD1d, CXCL12, and/or MICA.
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页数:13
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