title: MyD88 Adaptor-Dependent Microbial Sensing by Regulatory T Cells Promotes Mucosal Tolerance and Enforces Commensalism.
abstract: Commensal microbiota promote mucosal tolerance in part by engaging regulatory T (Treg) cells via Toll-like receptors (TLRs). We report that Treg-cell-specific deletion of the TLR adaptor MyD88 resulted in deficiency of intestinal Treg cells, a reciprocal increase in T helper 17 (Th17) cells and heightened interleukin-17 (IL-17)-dependent inflammation in experimental colitis. It also precipitated dysbiosis with overgrowth of segmented filamentous bacteria (SFB) and increased microbial loads in deep tissues. The Th17 cell dysregulation and bacterial dysbiosis were linked to impaired anti-microbial intestinal IgA responses, related to defective MyD88 adaptor- and Stat3 transcription factor-dependent T follicular regulatory and helper cell differentiation in the Peyer's patches. These findings establish an essential role for MyD88-dependent microbial sensing by Treg cells in enforcing mucosal tolerance and maintaining commensalism by promoting intestinal Treg cell formation and anti-commensal IgA responses.
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Charbonnier
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Noval Rivas
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Georgiev
authors.affiliation: Center for Clinical and Translational Metagenomics, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Center for Clinical and Translational Metagenomics, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Georg
authors.initials: G
authors.lastname: Gerber
authors.affiliation: Center for Clinical and Translational Metagenomics, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Bry
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: talal.chatila@childrens.harvard.edu.
authors.forename: Talal A
authors.initials: TA
authors.lastname: Chatila
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013559:Symbiosis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D050796:STAT3 Transcription Factor; D051193:Toll-Like Receptors