한빛사논문
- 조회1,075
Dongeon Kim1,2,4*, Mingyo Kim1,5*, Tae Woo Kim1,3*, Yong-ho Choe5*, Hae Sook Noh5, Hyun Min Jeon5, HyunSeok Kim1, Youngeun Lee1, Gayeong Hur1,6, Kyung-Mi Lee7, Kihyuk Shin8,9, Sang-il Lee5, and Seung-Hyo Lee1,2,3
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea; 2Biomedical Science and Engineering Interdisciplinary Program, Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon, South Korea; 3KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea; 4VA Palo Alto Health Care System, Stanford University School of Medicine, Stanford, CA; 5Division of Rheumatology, Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, South Korea; 6R&D Division, GenoFocus Inc., Daejeon, South Korea; 7Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea; 8Department of Dermatology, Pusan National University Yangsan Hospital, Yangsan, South Korea; 9Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
*D. Kim, M. Kim, T.W. Kim, and Y.-h. Choe contributed equally to this paper.
Correspondence to Seung-Hyo Lee, Sang-il Lee, Kihyuk Shin
Abstract
Lymph node fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impact of LN-FRCs on naive CD4+ T cell differentiation has not been explored. Here, we show that T cell zone FRCs of LNs (LN-TRCs) express CD25, the α chain of the IL-2 receptor heterotrimer. Moreover, LN-TRCs trans-present IL-2 to naive CD4+ T cells through CD25, thereby facilitating early IL-2–mediated signaling. CD25-deficient LN-TRCs exhibit attenuated STAT5 phosphorylation in naive CD4+ T cells during T cell differentiation, promoting T helper 17 (Th17) cell differentiation and Th17 response-related gene expression. In experimental autoimmune disease models, disease severity was elevated in mice lacking CD25 in LN-TRCs. Therefore, our results suggest that CD25 expression on LN-TRCs regulates CD4+ T cell differentiation by modulating early IL-2 signaling of neighboring, naive CD4+ T cells, influencing the overall properties of immune responses.
논문정보
- Research article
- 2022년 03월 (BRIC 등록일 2022-05-12)
- 국내(교신)+국외 연구진
- 생명과학 > 면역학
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