Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses

Nat Immunol. 2023 Apr;24(4):625-636. doi: 10.1038/s41590-023-01447-8. Epub 2023 Mar 20.


The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colon
  • Intestines*
  • Lectins, C-Type*
  • Receptors, Antigen, T-Cell, gamma-delta
  • Signal Transduction


  • dectin 1
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell, gamma-delta