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- Title
The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function.
- Authors
Oftedal, Bergithe E.; Maio, Stefano; Handel, Adam E.; White, Madeleine P. J.; Howie, Duncan; Davis, Simon; Prevot, Nicolas; Rota, Ioanna A.; Deadman, Mary E.; Kessler, Benedikt M.; Fischer, Roman; Trede, Nikolaus S.; Sezgin, Erdinc; Maizels, Rick M.; Holländer, Georg A.
- 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. Oftedal et al. generate mice lacking the chaperonin subunit CCT8 in T cells. They find that loss of CCT8 leads to reduced formation of nuclear actin filaments, changes in proteostasis, defective Th2 cell polarization and T cell metabolism and a failed antigenic response to intestinal helminths.
- Subjects
MOLECULAR chaperones; T cells; THYMOCYTES; HELMINTHS; INTESTINAL parasites
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02203-0