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Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males

Authors :
Hadi Abou-El-Hassan
Rafael M. Rezende
Saef Izzy
Galina Gabriely
Taha Yahya
Bruna K. Tatematsu
Karl J. Habashy
Juliana R. Lopes
Gislane L. V. de Oliveira
Amir-Hadi Maghzi
Zhuoran Yin
Laura M. Cox
Rajesh Krishnan
Oleg Butovsky
Howard L. Weiner
Source :
Nature Communications, Vol 14, Iss 1, Pp 1-19 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

Abstract Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. The innate and adaptive immune responses play an important role in the pathogenesis of TBI. Gamma-delta (γδ) T cells have been shown to affect brain immunopathology in multiple different conditions, however, their role in acute and chronic TBI is largely unknown. Here, we show that γδ T cells affect the pathophysiology of TBI as early as one day and up to one year following injury in a mouse model. TCRδ−/− mice are characterized by reduced inflammation in acute TBI and improved neurocognitive functions in chronic TBI. We find that the Vγ1 and Vγ4 γδ T cell subsets play opposing roles in TBI. Vγ4 γδ T cells infiltrate the brain and secrete IFN-γ and IL-17 that activate microglia and induce neuroinflammation. Vγ1 γδ T cells, however, secrete TGF-β that maintains microglial homeostasis and dampens TBI upon infiltrating the brain. These findings provide new insights on the role of different γδ T cell subsets after brain injury and lay down the principles for the development of targeted γδ T-cell-based therapy for TBI.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.6a5a1b424fcc41eabd0e3bb1b781dd2c
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-023-39857-9