| First Author | Valdor R | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 11 | Pages | 1046-54 |
| PubMed ID | 25263126 | Mgi Jnum | J:260626 |
| Mgi Id | MGI:6142644 | Doi | 10.1038/ni.3003 |
| Citation | Valdor R, et al. (2014) Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation. Nat Immunol 15(11):1046-54 |
| abstractText | Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses. Consequently, deletion of the gene encoding LAMP-2A in T cells caused deficient in vivo responses to immunization or infection with Listeria monocytogenes. Impaired CMA activity also occurred in T cells with age, which negatively affected their function. Restoration of LAMP-2A in T cells from old mice resulted in enhancement of activation-induced responses. Our findings define a role for CMA in regulating T cell activation through the targeted degradation of negative regulators of T cell activation. |
