CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

被引：574

作者：

Cheuk, Stanley ^{[1
]}

Schlums, Heinrich ^{[2
]}

Serezal, Irene Gallais ^{[1
,3
]}

Martini, Elisa ^{[1
]}

Chiang, Samuel C. ^{[2
]}

Marquardt, Nicole ^{[3
]}

Gibbs, Anna ^{[1
]}

Detlofsson, Ebba ^{[1
]}

Introini, Andrea ^{[1
]}

Forkel, Marianne ^{[3
]}

Hoog, Charlotte ^{[4
]}

Tjernlund, Annelie ^{[1
]}

Michaelsson, Jakob ^{[3
]}

Folkersen, Lasse ^{[5
]}

Mjosberg, Jenny ^{[3
]}

Blomqvist, Lennart ^{[6
]}

Ehrstrom, Marcus ^{[7
]}

Stahle, Mona ^{[1
,3
]}

Bryceson, Yenan T. ^{[2
,8
]}

Eidsmo, Liv ^{[1
,3
]}

机构：

[1] Karolinska Inst, Dept Med Solna, S-17177 Stockholm, Sweden

[2] Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med Huddinge, S-17177 Stockholm, Sweden

[3] Karolinska Univ Hosp, Dept Dermatol, S-14186 Stockholm, Sweden

[4] Karolinska Inst, Unit Inflammat Gastroenterol & Rheumatol, Dept Med, Huddinge, S-17177 Stockholm, Sweden

[5] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, Bldg 208, DK-2800 Lyngby, Denmark

[6] Karolinska Inst, Dept Med, Unit Endocrinol & Diabet, Huddinge, S-17177 Stockholm, Sweden

[7] Karolinska Univ, Hosp Solna, Dept Reconstruct Plast Surg, S-17176 Stockholm, Sweden

[8] Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, N-5021 Bergen, Norway

来源：

IMMUNITY | 2017年 / 46卷 / 02期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

MEMORY; IMMUNITY; INFECTION; VITILIGO; MAINTENANCE; PROTECTION; PATHWAY; TRIGGER; GAMMA; RNA;

D O I：

10.1016/j.immuni.2017.01.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-g, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8(+)CD49a(+) Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8(+)CD49a(-) Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8(+) Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.

引用

页码：287 / 300

页数：14

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