The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function

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
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
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173801Helminths and the Immune System: Regulation, Regulators and ImmunityRichard MaizelsWellcome Trust (WELLCOTR)106122/A/14/ZInstitute of Infection, Immunity & Inflammation
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZIII - Parasitology