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연세대학교, 굳티셀

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Nat. Commun., Sep 04 2023, 14 (1) | https://doi.org/10.1038/s41467-023-40986-4 Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis.

Jae-Seung Moon ^1,9,11, Chun-Chang Ho ^1,10,11, Jong-Hyun Park ^2,3, Kyungsoo Park ⁴, Bo-Young Shin ^1,10, Su-Hyeon Lee ¹, Ines Sequeira ⁵, Chin Hee Mun ⁶, Jin-Su Shin ^1,10, Jung-Ho Kim ⁷, Beom Seok Kim ⁷, Jin-Wook Noh ⁷, Eui-Seon Lee ⁷, Ji Young Son⁷, Yuna Kim ¹, Yeji lee ⁷, Hee Cho ¹, SunHyeon So ⁷, Jiyoon Park ¹, Eunsu Choi ⁷, Jong-Won Oh ¹, Sang-Won Lee⁶, Tomohiro Morio ⁸, Fiona M. Watt ⁵, Rho Hyun Seong ⁴ & Sang-Kyou Lee ^1,7,*

¹Department of Biotechnology, Yonsei University College of Life Science and Biotechnology, Seoul, Republic of Korea.
²Center for Brain Disorders, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.
³Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, Republic of Korea.
⁴Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea.
⁵Center for Stem Cells and Regenerative Medicine, King’s College London, Guy’s Hospital, London, UK.
⁶Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁷Good T cells, Inc., Seoul, Republic of Korea.
⁸Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁹Present address: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰Present address: Good T cells, Inc., Seoul, Republic of Korea.
¹¹These authors contributed equally: Jae-Seung Moon, Chun-Chang Ho.

^*Corresponding author: correspondence to Sang-Kyou Lee

Abstract

Regulatory T cells (T_reg) are CD4⁺ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4⁺ T cells, T_reg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1⁺ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1^- subpopulation. Lrig1-deficiency impairs the suppressive function of T_reg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4⁺Lrig1⁺ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-07)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

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