title: MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health.
abstract: Altered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remain unknown. Here, we report that signaling through the innate adaptor MyD88 in gut T cells coordinates germinal center responses, including TFH and IgA+ B cell development. TFH development is deficient in germ-free mice and can be restored by feeding TLR2 agonists that activate T cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to control the bacterial community, leading to worsened disease. Our findings identify that T cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis.
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Kubinak
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Charisse
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: W Zac
authors.initials: WZ
authors.lastname: Stephens
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Soto
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Bake
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
authors.affiliation: Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. Electronic address: june.round@path.utah.edu.
authors.forename: June L
authors.initials: JL
authors.lastname: Round
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006706:Homeostasis; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88