Ontogenic timing, T cell receptor signal strength, and Notch signaling direct γδ T cell functional differentiation in vivo.

Autor:	Chen ELY; Sunnybrook Research Institute, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada., Lee CR; Sunnybrook Research Institute, Toronto, ON, Canada., Thompson PK; Sunnybrook Research Institute, Toronto, ON, Canada., Wiest DL; Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, PA, USA., Anderson MK; Sunnybrook Research Institute, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada., Zúñiga-Pflücker JC; Sunnybrook Research Institute, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada. Electronic address: jczp@sri.utoronto.ca.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Jun 08; Vol. 35 (10), pp. 109227.
DOI:	10.1016/j.celrep.2021.109227
Abstrakt:	γδ T cells form an integral arm of the immune system and are critical during protective and destructive immunity. However, how γδ T cells are functionally programmed in vivo remains unclear. Here, we employ RBPJ-inducible and KN6-transgenic mice to assess the roles of ontogenic timing, T cell receptor (TCR) signal strength, and Notch signaling. We find skewing of Vγ1 + cells toward the PLZF + Lin28b + lineage at the fetal stage. Generation of interleukin-17 (IL-17)-producing γδ T cells is favored during, although not exclusive to, the fetal stage. Surprisingly, Notch signaling is dispensable for peripheral γδ T cell IL-17 production. Strong TCR signals, together with Notch, promote IL-4 differentiation. Conversely, less strong TCR signals promote Notch-independent IL-17 differentiation. Single-cell transcriptomic analysis reveals differential programming instilled by TCR signal strength and Notch for specific subsets. Thus, our results precisely define the roles of ontogenic timing, TCR signal strength, and Notch signaling in γδ T cell functional programming in vivo. Competing Interests: Declaration of interests J.C.Z.-P. is a co-founder and chair of the Scientific Advisory Board of Notch Therapeutics. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu