Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Foxp3+ Treg cells in humoral immunity.
J. B. Wing and S. Sakaguchi (2014)
Int. Immunol. 26, 61-69
   Abstract »    Full Text »    PDF »
Visualizing developmentally programmed endoreplication in mammals using ubiquitin oscillators.
A. Sakaue-Sawano, T. Hoshida, M. Yo, R. Takahashi, K. Ohtawa, T. Arai, E. Takahashi, S. Noda, H. Miyoshi, and A. Miyawaki (2013)
Development 140, 4624-4632
   Abstract »    Full Text »    PDF »
Activation of B cells by non-canonical helper signals.
A. Cerutti, M. Cols, and I. Puga (2012)
EMBO Rep. 13, 798-810
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882