| First Author | Mocholi E | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 5 | Pages | 1136-1150 |
| PubMed ID | 30067971 | Mgi Jnum | J:270701 |
| Mgi Id | MGI:6278641 | Doi | 10.1016/j.celrep.2018.06.065 |
| Citation | Mocholi E, et al. (2018) Autophagy Is a Tolerance-Avoidance Mechanism that Modulates TCR-Mediated Signaling and Cell Metabolism to Prevent Induction of T Cell Anergy. Cell Rep 24(5):1136-1150 |
| abstractText | In response to activation, CD4(+) T cells upregulate autophagy. However, the functional consequences of that upregulation have not been fully elucidated. In this study, we identify autophagy as a tolerance-avoidance mechanism. Our data show that inhibition of autophagy during CD4(+) T cell activation induces a long-lasting state of hypo-responsiveness that is accompanied by the expression of an anergic gene signature. Cells unable to induce autophagy after T cell receptor (TCR) engagement show inefficient mitochondrial respiration and decreased turnover of the protein tyrosine phosphatase PTPN1, which translates into defective TCR-mediated signaling. In vivo, inhibition of autophagy during antigen priming induces T cell anergy and decreases the severity of disease in an experimental autoimmune encephalomyelitis mouse model. Interestingly, CD4(+) T cells isolated from the synovial fluid of juvenile idiopathic arthritis patients, while resistant to suboptimal stimulation-induced anergy, can be tolerized with autophagy inhibitors. We propose that autophagy constitutes a tolerance-avoidance mechanism, which determines CD4(+) T cell fate. |
