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Myocardial infarction primes autoreactive T cells through activation of dendritic cells

Authors
  • Van Der Borght, Katrien
  • Scott, Charlotte
  • Nindl, Veronika
  • Bouché, Ann
  • Martens, Liesbet
  • Sichien, Dorine
  • Van Moorleghem, Justine
  • Vanheerswynghels, Manon
  • De Prijck, Sofie
  • Saeys, Yvan
  • Ludewig, Burkhard
  • Gillebert, Thierry
  • Guilliams, Martin
  • Carmeliet, Peter
  • Lambrecht, Bart
Publication Date
Jan 01, 2017
Source
Ghent University Institutional Archive
Keywords
Language
English
License
Unknown
External links

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 alpha-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) gamma-producing effector cells. Thus, cardiac-specific autoreactive T cells get activated by mature DCs following myocardial infarction.

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