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The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.11.246215v1?rss=1
Authors: Oftedal, B. E., Maio, S., Handel, A., White, M. P., Howie, D., Davis, S., Prevot, N., Rota, I. A., Deadman, M. E., Kessler, B. M., Fisher, R., Trede, N. S., Sezgin, E., Maizels, R. M., Hollander, G. 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. Additionally, Th2 polarization digresses in the absence of CCT-controlled protein folding resulting paradoxically in continued IFN-gamma 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.
Copy rights belong to original authors. Visit the link for more info
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.11.246215v1?rss=1
Authors: Oftedal, B. E., Maio, S., Handel, A., White, M. P., Howie, D., Davis, S., Prevot, N., Rota, I. A., Deadman, M. E., Kessler, B. M., Fisher, R., Trede, N. S., Sezgin, E., Maizels, R. M., Hollander, G. 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. Additionally, Th2 polarization digresses in the absence of CCT-controlled protein folding resulting paradoxically in continued IFN-gamma 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.
Copy rights belong to original authors. Visit the link for more info