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Myocardial infarction primes autoreactive T cells through activation of dendritic cells

(2017) CELL REPORTS. 18(12). p.3005-3017
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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.
Keywords
CARDIAC MACROPHAGES, APOPTOTIC CELLS, INNATE IMMUNITY, HEART-DISEASE, STEADY-STATE, ALPHA-MYOSIN, RAT-HEART, AUTOIMMUNITY, TOLERANCE, DIFFERENTIATION

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Chicago
Van Der Borght, Katrien, Charlotte Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, et al. 2017. “Myocardial Infarction Primes Autoreactive T Cells Through Activation of Dendritic Cells.” Cell Reports 18 (12): 3005–3017.
APA
Van Der Borght, K., Scott, C., Nindl, V., Bouché, A., Martens, L., Sichien, D., Van Moorleghem, J., et al. (2017). Myocardial infarction primes autoreactive T cells through activation of dendritic cells. CELL REPORTS, 18(12), 3005–3017.
Vancouver
1.
Van Der Borght K, Scott C, Nindl V, Bouché A, Martens L, Sichien D, et al. Myocardial infarction primes autoreactive T cells through activation of dendritic cells. CELL REPORTS. 2017;18(12):3005–17.
MLA
Van Der Borght, Katrien, Charlotte Scott, Veronika Nindl, et al. “Myocardial Infarction Primes Autoreactive T Cells Through Activation of Dendritic Cells.” CELL REPORTS 18.12 (2017): 3005–3017. Print.
@article{8521884,
  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.},
  author       = {Van Der Borght, Katrien and Scott, Charlotte and Nindl, Veronika and Bouch{\'e}, Ann and Martens, Liesbet and Sichien, Dorine and Van Moorleghem, Justine and Vanheerswynghels, Manon and De Prijck, Sofie and Saeys, Yvan and Ludewig, Burkhard and Gillebert, Thierry and Guilliams, Martin and Carmeliet, Peter and Lambrecht, Bart},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  language     = {eng},
  number       = {12},
  pages        = {3005--3017},
  title        = {Myocardial infarction primes autoreactive T cells through activation of dendritic cells},
  url          = {http://dx.doi.org/10.1016/j.celrep.2017.02.079},
  volume       = {18},
  year         = {2017},
}

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