A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota.
A T cell receptor transgenic mouse line reactive to a microbiota flagellin, CBir1, was used to define mechanisms of host microbiota homeostasis. Intestinal IgA, but not serum IgA, was found to block mucosal flagellin uptake and systemic T cell activation in mice. Depletion of CD4(+)CD25(+) Tregs decreased IgA(+) B cells, total IgA, and CBir1-specific IgA in gut within days. Repletion of T cell-deficient mice with either CD4(+)CD25(+) or CD4(+)foxp3(+) Tregs restored intestinal IgA to a much greater extent than their reciprocal CD4(+) subsets, indicating that Tregs are the major helper cells for IgA responses to microbiota antigens such as flagellin. We propose that the major role of this coordinated Treg-IgA response is to maintain commensalism with the microbiota.
Cong
Yingzi
Y
Departments of Medicine and Microbiology, Pediatric Dentistry, and Genetics, University of Alabama at Birmingham, AL 35294, USA. ycong@uab.edu
Feng
Ting
T
Fujihashi
Kohtaro
K
Schoeb
Trenton R
TR
Elson
Charles O
CO
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005408:Flagellin / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000942:Antigens, Bacterial; C502160:CBir1 flagellin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007070:Immunoglobulin A; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005408:Flagellin