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

Stanley Cheuk; Heinrich Schlums; Irène Gallais Sérézal; Elisa Martini; Samuel C. Chiang; Nicole Marquardt; Anna Gibbs; Ebba Detlofsson; Andrea Introini; Marianne Forkel; Charlotte Höög; Annelie Tjernlund; Jakob Michaelsson; Lasse Westergaard Folkersen; Jenny Mjösberg; Lennart Blomqvist; Marcus Ehrström; Mona Ståhle; Yenan T. Bryceson; Liv Eidsmo

doi:10.1016/j.immuni.2017.01.009

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

Stanley Cheuk
, Heinrich Schlums
, Irène Gallais Sérézal
, Elisa Martini
, Samuel C. Chiang
, Nicole Marquardt
, Anna Gibbs
, Ebba Detlofsson
, Andrea Introini
, Marianne Forkel
, Charlotte Höög
, Annelie Tjernlund
, Jakob Michaelsson
, Lasse Westergaard Folkersen
, Jenny Mjösberg
, Lennart Blomqvist
, Marcus Ehrström
, Mona Ståhle
, Yenan T. Bryceson
, Liv Eidsmo

Karolinska Institutet
Karolinska University Hospital
University of Bergen

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

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-γ, 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.

Original language	English
Journal	Immunity
Volume	46
Issue number	2
Pages (from-to)	287-300
ISSN	1074-7613
DOIs	https://doi.org/10.1016/j.immuni.2017.01.009
Publication status	Published - 2017

Bibliographical note

Open Access funded by European Research Council
Under a Creative Commons license

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.immuni.2017.01.009

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Cheuk, S., Schlums, H., Sérézal, I. G., Martini, E., Chiang, S. C., Marquardt, N., Gibbs, A., Detlofsson, E., Introini, A., Forkel, M., Höög, C., Tjernlund, A., Michaelsson, J., Folkersen, L. W., Mjösberg, J., Blomqvist, L., Ehrström, M., Ståhle, M., Bryceson, Y. T., & Eidsmo, L. (2017). CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin. Immunity, 46(2), 287-300. https://doi.org/10.1016/j.immuni.2017.01.009

@article{93bec52737c2402288d189c6b68234a5,

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

abstract = "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-γ, 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.",

author = "Stanley Cheuk and Heinrich Schlums and S{\'e}r{\'e}zal, \{Ir{\`e}ne Gallais\} and Elisa Martini and Chiang, \{Samuel C.\} and Nicole Marquardt and Anna Gibbs and Ebba Detlofsson and Andrea Introini and Marianne Forkel and Charlotte H{\"o}{\"o}g and Annelie Tjernlund and Jakob Michaelsson and Folkersen, \{Lasse Westergaard\} and Jenny Mj{\"o}sberg and Lennart Blomqvist and Marcus Ehrstr{\"o}m and Mona St{\aa}hle and Bryceson, \{Yenan T.\} and Liv Eidsmo",

note = "Open Access funded by European Research Council Under a Creative Commons license",

year = "2017",

doi = "10.1016/j.immuni.2017.01.009",

language = "English",

volume = "46",

pages = "287--300",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

Cheuk, S, Schlums, H, Sérézal, IG, Martini, E, Chiang, SC, Marquardt, N, Gibbs, A, Detlofsson, E, Introini, A, Forkel, M, Höög, C, Tjernlund, A, Michaelsson, J, Folkersen, LW, Mjösberg, J, Blomqvist, L, Ehrström, M, Ståhle, M, Bryceson, YT & Eidsmo, L 2017, 'CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin', Immunity, vol. 46, no. 2, pp. 287-300. https://doi.org/10.1016/j.immuni.2017.01.009

TY - JOUR

T1 - CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

AU - Cheuk, Stanley

AU - Schlums, Heinrich

AU - Sérézal, Irène Gallais

AU - Martini, Elisa

AU - Chiang, Samuel C.

AU - Marquardt, Nicole

AU - Gibbs, Anna

AU - Detlofsson, Ebba

AU - Introini, Andrea

AU - Forkel, Marianne

AU - Höög, Charlotte

AU - Tjernlund, Annelie

AU - Michaelsson, Jakob

AU - Folkersen, Lasse Westergaard

AU - Mjösberg, Jenny

AU - Blomqvist, Lennart

AU - Ehrström, Marcus

AU - Ståhle, Mona

AU - Bryceson, Yenan T.

AU - Eidsmo, Liv

N1 - Open Access funded by European Research Council Under a Creative Commons license

PY - 2017

Y1 - 2017

N2 - 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-γ, 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.

AB - 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-γ, 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.

U2 - 10.1016/j.immuni.2017.01.009

DO - 10.1016/j.immuni.2017.01.009

M3 - Journal article

C2 - 28214226

SN - 1074-7613

VL - 46

SP - 287

EP - 300

JO - Immunity

JF - Immunity

IS - 2

ER -

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

Abstract

Bibliographical note

UN SDGs

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