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Science 336 (6080): 485-489

Copyright © 2012 by the American Association for the Advancement of Science

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

Shimpei Kawamoto,1,* Thinh H. Tran,1,2,* Mikako Maruya,1,* Keiichiro Suzuki,1,3 Yasuko Doi,1 Yumi Tsutsui,1 Lucia M. Kato,1,4 Sidonia Fagarasan1,{dagger}

Abstract: 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.

1 Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama 1-7-22, Tsurumi, Yokohama 230-0045, Japan.
2 Department of Biochemistry, Hanoi Medical University, 1st Ton That Tung, Hanoi, Vietnam.
3 AK project, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.
4 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sidonia-f{at}rcai.riken.jp

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