The Inhibitory Receptor PD-1 Regulates IgA Selection and Bacterial Composition in the Gut

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Science  27 Apr 2012:
Vol. 336, Issue 6080, pp. 485-489
DOI: 10.1126/science.1217718

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Immunoglobulin A (IgA) is essential to maintain the symbiotic balance between gut bacterial communities and the host immune system. Here we provide evidence that the inhibitory co-receptor programmed cell death–1 (PD-1) regulates the gut microbiota through appropriate selection of IgA plasma cell repertoires. PD-1 deficiency generates an excess number of T follicular helper (TFH) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer’s patches. Consequently, the IgAs produced in PD-1–deficient mice have reduced bacteria-binding capacity, which causes alterations of microbial communities in the gut. Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier.

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