Cell Reports | |
Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells | |
Thierry Gillebert1  Sofie De Prijck2  Justine Van Moorleghem2  Dorine Sichien2  Martin Guilliams2  Manon Vanheerswynghels2  Charlotte L. Scott2  Liesbet Martens2  Katrien Van der Borght2  Yvan Saeys2  Bart N. Lambrecht2  Burkhard Ludewig3  Veronika Nindl3  Ann Bouché4  Peter Carmeliet4  | |
[1] Department of Internal Medicine, Ghent University, 9000 Ghent, Belgium;Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, 9052 Ghent, Belgium;Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland;VIB Vesalius Research Center, 3000 Leuven, Belgium; | |
关键词: dendritic cell; heart; tolerance; autoimmunity; myocardial infarction; tissue necrosis; IRF4; IRF8; cardiac myosin; gene expression; | |
DOI : 10.1016/j.celrep.2017.02.079 | |
来源: DOAJ |
【 摘 要 】
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs. In steady state, cardiac self-antigen α-myosin was presented in the heart-draining mediastinal lymph node (mLN) by cDC1s, driving the proliferation of antigen-specific CD4+ TCR-M T cells and their differentiation into regulatory cells (Tregs). Following MI, all DC subsets infiltrated the heart, whereas only cDCs migrated to the mLN. Here, cDC2s induced TCR-M proliferation and differentiation into interleukin-(IL)-17/interferon-(IFN)γ-producing effector cells. Thus, cardiac-specific autoreactive T cells get activated by mature DCs following myocardial infarction.
【 授权许可】
Unknown