한빛사
>
한빛사논문
한빛사논문
- 조회3,889
Nat. Immunol., Published: 30 April 2018 | doi:10.1038/s41590-018-0102-6
Atherogenic dyslipidemia promotes autoimmune follicular helper T cell responses via IL-27
Heeju Ryu1,2, Hoyong Lim1, Garam Choi1,2, Young-Jun Park1,2, Minkyoung Cho1, Hyeongjin Na1,2, Chul Won Ahn2,3, Young Chul Kim2,3, Wan-Uk Kim4, Sang-Hak Lee5 and Yeonseok Chung1,2*
1Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea. 2BK21 Plus program, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. 3Laboratory of Toxicology, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. 4Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea. 5Division of Cardiology, Department of Internal Medicine, Severance Hospital, College of Medicine, Yonsei University, Seoul, Republic of Korea.
*Correspondence to Yeonseok Chung
1Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea. 2BK21 Plus program, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. 3Laboratory of Toxicology, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. 4Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea. 5Division of Cardiology, Department of Internal Medicine, Severance Hospital, College of Medicine, Yonsei University, Seoul, Republic of Korea.
*Correspondence to Yeonseok Chung
Abstract
The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe-/- and Ldlr-/- mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe-/- mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c. Mechanistically, the atherogenic environment induced the cytokine IL-27 from dendritic cells in a Toll-like receptor 4 (TLR4)-dependent manner, which in turn triggered the differentiation of CXCR3+ TFH cells while inhibiting the differentiation of follicular regulatory T cells. Blockade of IL-27 signals diminished the increased TFH cell responses in atherogenic mice. Thus, atherogenic dyslipidemia augments autoimmune TFH cell responses and subsequent IgG2c production in a TLR4- and IL-27-dependent manner.
논문정보
- Research article
- 2018년 04월 (BRIC 등록일 2018-05-10)
- 국내 연구진
- 생명과학 > 면역학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
