title: Inflammatory T helper 17 cells promote depression-like behavior in mice.
abstract: BACKGROUND
  Recognition of substantial immune-neural interactions is revising dogmas about their insular actions and revealing that immune-neural interactions can substantially impact central nervous system functions. The inflammatory cytokine interleukin-6 promotes susceptibility to depression and drives production of inflammatory T helper 17 (Th17) T cells, raising the hypothesis that in mouse models, Th17 cells promote susceptibility to depression-like behaviors.
  
  
  METHODS
  Behavioral characteristics were measured in male mice administered Th17 cells, CD4(+) cells, or vehicle and in retinoid-related orphan receptor-γT (RORγT)(+/GFP) mice or male mice treated with RORγT inhibitor or anti-interleukin-17A antibodies.
  
  
  RESULTS
  Mouse brain Th17 cells were elevated by learned helplessness and chronic restraint stress, two common depression-like models. Th17 cell administration promoted learned helplessness in 89% of mice in a paradigm where no vehicle-treated mice developed learned helplessness, and impaired novelty suppressed feeding and social interaction behaviors. Mice deficient in the RORγT transcription factor necessary for Th17 cell production exhibited resistance to learned helplessness, identifying modulation of RORγT as a potential intervention. Treatment with the RORγT inhibitor SR1001, or anti-interleukin-17A antibodies to abrogate Th17 cell function, reduced Th17-dependent learned helplessness.
  
  
  CONCLUSIONS
  These findings indicate that Th17 cells are increased in the brain during depression-like states, promote depression-like behaviors in mice, and specifically inhibiting the production or function of Th17 cells reduces vulnerability to depression-like behavior, suggesting antidepressant effects may be attained by targeting Th17 cells.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, and Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. ebeurel@med.miami.edu
authors.forename: Eléonore
authors.initials: E
authors.lastname: Beurel
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Harrington
authors.forename: Richard S
authors.initials: RS
authors.lastname: Jope
mesh_terms: D000818:Animals; D003863:Depression / Q000150:complications / Q000276:immunology* / Q000523:psychology; D055879:Gene Knock-In Techniques; D006380:Helplessness, Learned; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000037:antagonists & inhibitors / Q000235:genetics; D012149:Restraint, Physical / Q000523:psychology; D013449:Sulfonamides / Q000494:pharmacology; D058504:Th17 Cells / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C558809:SR1001; D013449:Sulfonamides; D013844:Thiazoles