Publication: Chaperone mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation
Authors
Mocholi, Enric ; Botbol, Yair ; Guerrero Ros, Ignacio ; Dinesh, Chandra ; Koga, Hiroshi ; Gravekamp, Claudia ; Cuervo, Ana María ; Macián, Fernando ; Valdor Alonso, Rut
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/ni.3003
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info:eu-repo/semantics/article
Description
© 2014 Nature America, Inc. This document is the Published Manuscript version of a Published Work that appeared in final form in Nature Immunology. To access the final edited and published work see https://doi.org/10.1038/ni.3003
Abstract
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.
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Citation
Nature Immunology, 2014, Vol. 15, pp. 1046–1054
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1-ene-2999
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