title: Tissue-expressed B7-H1 critically controls intestinal inflammation.
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.
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Lisa
authors: L
authors: Scandiuzzi
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Kaya
authors: K
authors: Ghosh
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Kimberly A
authors: KA
authors: Hofmeyer
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Yael M
authors: YM
authors: Abadi
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Eszter
authors: E
authors: Lázár-Molnár
authors: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Elaine Y
authors: EY
authors: Lin
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Qiang
authors: Q
authors: Liu
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Hyungjun
authors: H
authors: Jeon
authors: Department of Biochemistry, Physiology, and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Steven C
authors: SC
authors: Almo
authors: Department of Immunobiology and Yale Comprehensive Cancer Center, Yale University, New Haven, CT 06519, USA.
authors: Lieping
authors: L
authors: Chen
authors: 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.
authors: Stanley G
authors: SG
authors: Nathenson
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: xing-xing.zang@einstein.yu.edu.
authors: Xingxing
authors: X
authors: Zang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D061026:Programmed Cell Death 1 Receptor; D012967:Sodium Dodecyl Sulfate; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22