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Science. 2012 Apr 27;336(6080):485-9. doi: 10.1126/science.1217718.

The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut.

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Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama, Tsurumi, Yokohama, Japan.


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 (T(FH)) 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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