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

Xiaolei Zhu, Shinji Sakamoto, Chiharu Ishii, Matthew D. Smith, Koki Ito, Mizuho Obayashi, Lisa Unger, Yuto Hasegawa, Shunya Kurokawa, Taishiro Kishimoto, Hui Li, Shinya Hatano, Tza Huei Wang, Yasunobu Yoshikai, Shin ichi Kano, Shinji Fukuda, Kenji Sanada, Peter A. Calabresi, Atsushi Kamiya

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)625-636
Number of pages12
JournalNature Immunology
Volume24
Issue number4
DOIs
StatePublished - Apr 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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