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Cell Rep. 2014 Feb 27;6(4):625-32. doi: 10.1016/j.celrep.2014.01.020. Epub 2014 Feb 13.

Tissue-expressed B7-H1 critically controls intestinal inflammation.

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
3
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
4
Department of Biochemistry, Physiology, and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
5
Department of Immunobiology and Yale Comprehensive Cancer Center, Yale University, New Haven, CT 06519, USA.
6
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
7
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: xing-xing.zang@einstein.yu.edu.

Abstract

B7-H1 (PD-L1) on immune cells plays an important role in T cell coinhibition by binding its receptor PD-1. Here, we show that both human and mouse intestinal epithelium express B7-H1 and that B7-H1-deficient mice are highly susceptible to dextran sodium sulfate (DSS)- or trinitrobenzenesulfonic acid (TNBS)-induced gut injury. B7-H1 deficiency during intestinal inflammation leads to high mortality and morbidity, which are associated with severe pathological manifestations in the colon, including loss of epithelial integrity and overgrowth of commensal bacteria. Results from bone marrow chimeric and knockout mice show that B7-H1 expressed on intestinal parenchyma, but not on hematopoietic cells, controls intestinal inflammation in an adaptive immunity-independent fashion. Finally, we demonstrate that B7-H1 dampened intestinal inflammation by inhibiting tumor necrosis factor α (TNF-α) production and by stimulating interleukin 22 secretion from CD11c(+)CD11b(+) lamina propria cells. Thus, our data uncover a mechanism through which intestinal tissue-expressed B7-H1 functions as an essential ligand for innate immune cells to prevent gut inflammation.

PMID:
24529703
PMCID:
PMC3962725
DOI:
10.1016/j.celrep.2014.01.020
[Indexed for MEDLINE]
Free PMC Article

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