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Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells.

Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells.
Author Information (click to view)

Van der Borght K, Scott CL, Nindl V, Bouché A, Martens L, Sichien D, Van Moorleghem J, Vanheerswynghels M, De Prijck S, Saeys Y, Ludewig B, Gillebert T, Guilliams M, Carmeliet P, Lambrecht BN,


Van der Borght K, Scott CL, Nindl V, Bouché A, Martens L, Sichien D, Van Moorleghem J, Vanheerswynghels M, De Prijck S, Saeys Y, Ludewig B, Gillebert T, Guilliams M, Carmeliet P, Lambrecht BN, (click to view)

Van der Borght K, Scott CL, Nindl V, Bouché A, Martens L, Sichien D, Van Moorleghem J, Vanheerswynghels M, De Prijck S, Saeys Y, Ludewig B, Gillebert T, Guilliams M, Carmeliet P, Lambrecht BN,

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Cell reports 18(12) 3005-3017 pii 10.1016/j.celrep.2017.02.079

Abstract

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.

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