Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis

Jae-Seung Moon, Chun-Chang Ho, Jong-Hyun Park, Kyungsoo Park, Bo-Young Shin, Su-Hyeon Lee, Ines Sequeira, Chin Hee Mun, Jin-Su Shin, Jung-Ho Kim, Beom Seok Kim, Jin-Wook Noh, Eui-Seon Lee, Ji Young Son, Yuna Kim, Yeji Lee, Hee Cho, SunHyeon So, Jiyoon Park, Eunsu Choi, Jong-Won Oh, Sang-Won Lee, Tomohiro Morio, Fiona M. Watt, Rho Hyun Seong and Sang-Kyou Lee ()
Additional contact information
Jae-Seung Moon: Yonsei University College of Life Science and Biotechnology
Chun-Chang Ho: Yonsei University College of Life Science and Biotechnology
Jong-Hyun Park: Korea Institute of Science and Technology
Kyungsoo Park: Seoul National University
Bo-Young Shin: Yonsei University College of Life Science and Biotechnology
Su-Hyeon Lee: Yonsei University College of Life Science and Biotechnology
Ines Sequeira: King’s College London, Guy’s Hospital
Chin Hee Mun: Yonsei University College of Medicine
Jin-Su Shin: Yonsei University College of Life Science and Biotechnology
Jung-Ho Kim: Good T cells, Inc.
Beom Seok Kim: Good T cells, Inc.
Jin-Wook Noh: Good T cells, Inc.
Eui-Seon Lee: Good T cells, Inc.
Ji Young Son: Good T cells, Inc.
Yuna Kim: Yonsei University College of Life Science and Biotechnology
Yeji Lee: Good T cells, Inc.
Hee Cho: Yonsei University College of Life Science and Biotechnology
SunHyeon So: Good T cells, Inc.
Jiyoon Park: Yonsei University College of Life Science and Biotechnology
Eunsu Choi: Good T cells, Inc.
Jong-Won Oh: Yonsei University College of Life Science and Biotechnology
Sang-Won Lee: Yonsei University College of Medicine
Tomohiro Morio: Tokyo Medical and Dental University (TMDU)
Fiona M. Watt: King’s College London, Guy’s Hospital
Rho Hyun Seong: Seoul National University
Sang-Kyou Lee: Yonsei University College of Life Science and Biotechnology

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Regulatory T cells (Treg) 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, Treg 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 Treg 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.

Date: 2023
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DOI: 10.1038/s41467-023-40986-4

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