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

JL Kubinak, C Petersen, WZ Stephens, R Soto… - Cell host & …, 2015 - cell.com
JL Kubinak, C Petersen, WZ Stephens, R Soto, E Bake, RM O'Connell, JL Round
Cell host & microbe, 2015cell.com
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 (T FH) 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 T FH and IgA+ B cell development. T FH …
Summary
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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