| First Author | Van der Borght K | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 12 | Pages | 3005-3017 |
| PubMed ID | 28329691 | Mgi Jnum | J:265971 |
| Mgi Id | MGI:6103214 | Doi | 10.1016/j.celrep.2017.02.079 |
| Citation | Van der Borght K, et al. (2017) Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells. Cell Rep 18(12):3005-3017 |
| abstractText | 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. |
