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- Title
Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males.
- Authors
Abou-El-Hassan, Hadi; Rezende, Rafael M.; Izzy, Saef; Gabriely, Galina; Yahya, Taha; Tatematsu, Bruna K.; Habashy, Karl J.; Lopes, Juliana R.; de Oliveira, Gislane L. V.; Maghzi, Amir-Hadi; Yin, Zhuoran; Cox, Laura M.; Krishnan, Rajesh; Butovsky, Oleg; Weiner, Howard L.
- 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. Traumatic brain injury is not only a neurological but also an immunological condition in which multiple innate and adaptive immune cell types play roles. Here authors show in a mouse model that the Vγ4 subtype of the unconventional gamma-delta T cells promote neuroinflammation, while the Vγ1 subtype ameliorates immunopathology.
- Subjects
BRAIN injuries; T cells; IMMUNOPATHOLOGY; T cell receptors; HOMEOSTASIS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39857-9