Tissue-Expressed B7-H1 Critically Controls Intestinal Inflammation

Lisa Scandiuzzi, Kaya Ghosh, Kimberly A. Hofmeyer, Yael M. Abadi, Eszter Lázár-Molnár, Elaine Y. Lin, Qiang Liu, Hyungjun Jeon, Steven C. Almo, Lieping Chen, Stanley G. Nathenson, Xingxing Zang

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27 Scopus citations

Abstract

B7-H1 (PD-L1) on immune cells plays an important role in Tcell 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 mortalityand 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.

Original languageEnglish (US)
Pages (from-to)625-632
Number of pages8
JournalCell Reports
Volume6
Issue number4
DOIs
Publication statusPublished - Feb 14 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Scandiuzzi, L., Ghosh, K., Hofmeyer, K. A., Abadi, Y. M., Lázár-Molnár, E., Lin, E. Y., ... Zang, X. (2014). Tissue-Expressed B7-H1 Critically Controls Intestinal Inflammation. Cell Reports, 6(4), 625-632. https://doi.org/10.1016/j.celrep.2014.01.020