Oftedal, B. E. et al. (2021) The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function. Communications Biology, 4, 681. (doi: 10.1038/s42003-021-02203-0) (PMID:34083746) (PMCID:PMC8175432)
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Abstract
T cells rely for their development and function on the correct folding and turnover of proteins generated in response to a broad range of molecular cues. In the absence of the eukaryotic type II chaperonin complex, CCT, T cell activation induced changes in the proteome are compromised including the formation of nuclear actin filaments and the formation of a normal cell stress response. Consequently, thymocyte maturation and selection, and T cell homeostatic maintenance and receptor-mediated activation are severely impaired. In the absence of CCT-controlled protein folding, Th2 polarization diverges from normal differentiation with paradoxical continued IFN-γ expression. As a result, CCT-deficient T cells fail to generate an efficient immune protection against helminths as they are unable to sustain a coordinated recruitment of the innate and adaptive immune systems. These findings thus demonstrate that normal T cell biology is critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | White, Dr Madeleine and Maizels, Professor Rick |
Authors: | Oftedal, B. E., Maio, S., Handel, A. E., White, M. P.J., Howie, D., Davis, S., Prevot, N., Rota, I. A., Deadman, M. E., Kessler, B. M., Fischer, R., Trede, N. S., Sezgin, E., Maizels, R. M., and Holländer, G. A. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
Journal Name: | Communications Biology |
Publisher: | Nature Research |
ISSN: | 2399-3642 |
ISSN (Online): | 2399-3642 |
Copyright Holders: | Copyright © 2021 The Authors |
First Published: | First published in Communications Biology 4: 681 |
Publisher Policy: | Reproduced under a Creative Commons License |
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