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A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity

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Title
A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity
Author(s)
Seok, Joon; Cho, Sung-Dong; Lee, Jeongsoo; Choi, Yunseo; Kim, Su-Young; Lee, Sung-Min; Sang-Hoon Kim; Jeong, Seongju; Jeon, Minwoo; Hoyoung Lee; Kim, A. Reum; Choi, Baekgyu; Ha, Sang-Jun; Jung, Inkyung; Yoon, Ki-Jun; Park, Jong-Eun; Kim, Jong Hoon; Kim, Beom Joon; Eui-Cheol Shin; Park, Su-Hyung
Publication Date
2023-06
Journal
Nature Immunology, v.24, pp.1308 - 1317
Publisher
Nature Publishing Group
Abstract
Virtual memory T (TVM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although TVM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a TVM cell-originated CD44super-high(s-hi)CD49dlo CD8+ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8+ TVM cells and can cause alopecia areata. Mechanistically, CD44s-hiCD49dlo CD8+ T cells could be induced from conventional TVM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
URI
https://pr.ibs.re.kr/handle/8788114/14001
DOI
10.1038/s41590-023-01547-5
ISSN
1529-2908
Appears in Collections:
Korea Virus Research Institute(한국바이러스기초연구소) > Center for Viral Immunology(바이러스 면역 연구센터) > 1. Journal Papers (저널논문)
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