Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells.
IL-17 cytokine production by the Th17 T cell subset is regulated by intestinal commmensals. We show that microbial colonization also regulates innate IL-17 production. A population of CD62L(-) gamma/delta T cells, in particular a lineage expressing the IL-1 receptor 1 (IL-1R1), can be quickly activated by microbes to produce IL-17. Antibiotic treatment and monocolonization of mice suggest that specific commensals-but not metronidazole-sensitive anaerobes like Bacteroides species-are required for maintaining IL-1R1(+) gamma/delta T cells. Signaling through the guanine nucleotide exchange factor VAV1, but not through Toll-like receptors or antigen presentation pathways, is essential for inducing IL-1R1(+) gamma/delta T cells. Furthermore, IL-1R1(+) gamma/delta T cells are a potential source of IL-17 that can be activated by IL-23 and IL-1 in both infectious and noninfectious settings in vitro and in vivo. Thus, commensals orchestrate the expansion of phenotypically distinct gammadelta T cells, and innate immunity is a three-way interaction between host, pathogens, and microbiota.
Duan
Jinyou
J
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Chung
Hachung
H
Troy
Erin
E
Kasper
Dennis L
DL
D000818:Animals; D001419:Bacteria / Q000276:immunology*; D049109:Cell Proliferation; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D017472:Receptors, Interleukin-1 / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017472:Receptors, Interleukin-1