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Cell Host Microbe. 2015 Feb 11;17(2):153-63. doi: 10.1016/j.chom.2014.12.009. Epub 2015 Jan 22.

MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health.

Author information

1
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
2
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.

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.

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PMID:
25620548
PMCID:
PMC4451207
DOI:
10.1016/j.chom.2014.12.009
[Indexed for MEDLINE]
Free PMC Article

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