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Signaling via LTβR on the lamina propria stromal cells of the gut is required for IgA production

Nature Immunology volume 3, pages 576–582 (2002)Cite this article

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Abstract

Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) are thought to be essential for immunoglobulin A (IgA) production. We found that the severe IgA deficiency in lymphotoxin-deficient (LT−/−) mice could be fully reversed by reconstitution with LT-expressing bone marrow, despite the absence of both LNs and PPs. The number of IgA precursors from LT−/− mice was not reduced, and they were able to migrate into the lamina propria (LP) of wild-type mice but not of LTβR−/− mice. Consistently, lymphoid tissue chemokines and adhesion molecules were reduced within the LP of LTα−/− and LTβR−/− mice. IgA deficiency in LTα−/− mice was reversed by the transplantation of a segment of RAG-1 (recombination-activating gene 1)–deficient intestine, which confirmed the dispensability of the MLNs and PPs and the sufficiency of the LT-mediated gut microenvironment for IgA production.

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Figure 1: IgA expression requirements.
Figure 2: IgA production in lethally irradiated mice reconstituted with LT-deficient BM cells.
Figure 3: The number of B1 and IgA+ cells was normal in peritoneal cavity but was greatly reduced in the LP of LT-deficient mice.
Figure 4: Chemokine and adhesion molecule expression in the LP of LTα−/− mice.
Figure 5: Adoptive transfer of peritoneal cavity to WT or LTβR−/− recipients.
Figure 6: IgA-deficiency in LTα−/− mice can be rescued by the transplantation of RAG-1−/− gut.

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  • 20 May 2002

    Online figure was updated, PDF was ammended with note. Issue PDF contains "corrected 20 May 2002 (details online)" line.

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Acknowledgements

We thank the National Cell Culture Center for the LTβR-Ig. Supported in part by NIH grants (HD-37104 and DK-58897) and Biogen. LTβR−/− mice were kindly provided by K. Pfeffer (Technical University of Munich, Germany).

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Authors and Affiliations

  1. Department of Pathology and Committee on Immunology, The University of Chicago, 5841 S. Maryland, Chicago, 60637, IL, USA

    Hyung-Sik Kang, Robert K. Chin, Yang Wang, Ping Yu & Yang-Xin Fu

  2. Emory Transplant Center and Department of Surgery Emory University School of Medicine, Emory University School of Medicine, Atlanta, 30322, GA, USA

    Jun Wang & Kenneth A. Newell

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Correspondence to Yang-Xin Fu.

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Kang, HS., Chin, R., Wang, Y. et al. Signaling via LTβR on the lamina propria stromal cells of the gut is required for IgA production. Nat Immunol 3, 576–582 (2002). https://doi.org/10.1038/ni795

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