박수형 (KAIST 의과학대학원)

한빛사논문

조회637

KAIST 의과학대학원

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Nat. Immunol., 26 June 2023 | https://doi.org/10.1038/s41590-023-01547-5 A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity

Joon Seok ^1,2,9, Sung-Dong Cho ^1,9, Jeongsoo Lee ¹, Yunseo Choi ¹, Su-Young Kim ², Sung-Min Lee ^3,4, Sang-Hoon Kim ⁵, Seongju Jeong ¹, Minwoo Jeon ¹, Hoyoung Lee ⁵, A. Reum Kim ¹, Baekgyu Choi ³, Sang-Jun Ha ⁶, Inkyung Jung ³, Ki-Jun Yoon ^3,4, Jong-Eun Park ¹, Jong Hoon Kim ⁷, Beom Joon Kim ², Eui-Cheol Shin ^1,5,* & Su-Hyung Park ^1,8,*

¹Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
²Department of Dermatology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
³Department of Biological Science, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
⁴KAIST Stem Cell Center, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
⁵The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
⁶Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
⁷Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁸The Center for Epidemic Preparedness, KAIST Institute, Daejeon, Republic of Korea.
⁹These authors contributed equally: Joon Seok, Sung-Dong Cho.

^*Corresponding author: correspondence to Eui-Cheol Shin or Su-Hyung Park

Abstract

Virtual memory T (T_VM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although T_VM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a T_VM cell-originated CD44^{super-high(s-hi)}CD49d^lo CD8⁺ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8⁺ T_VM cells and can cause alopecia areata. Mechanistically, CD44^s-hiCD49d^lo CD8⁺ T cells could be induced from conventional T_VM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44^s-hiCD49d^lo 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 T_VM cells can cause chronic inflammatory disease by innate-like cytotoxicity.

논문정보

형식Research article
게재일2023년 06월 (BRIC 등록일 2023-06-27)
연구진국내 연구진
분야 의약학 > 면역의학

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