TY - JOUR
T1 - Tissue-Expressed B7-H1 Critically Controls Intestinal Inflammation
AU - Scandiuzzi, Lisa
AU - Ghosh, Kaya
AU - Hofmeyer, Kimberly A.
AU - Abadi, Yael M.
AU - Lázár-Molnár, Eszter
AU - Lin, Elaine Y.
AU - Liu, Qiang
AU - Jeon, Hyungjun
AU - Almo, Steven C.
AU - Chen, Lieping
AU - Nathenson, Stanley G.
AU - Zang, Xingxing
N1 - Funding Information:
We thank the Flow Cytometry Core and the Histotechnology and Comparative Pathology Facility of Albert Einstein College of Medicine, Vera Des Marais for the assistance on Volocity software, and Jordan Chinai for reading the manuscript. This work was supported by NIH DP2DK083076, GM094665, AI007289, DOD PC094137, NIH P30CA013330, P60DK020541, AI51519, P30AG038072, T32DK007218, T32DK007513, and T32GM007491.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896696538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896696538&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2014.01.020
DO - 10.1016/j.celrep.2014.01.020
M3 - Article
C2 - 24529703
AN - SCOPUS:84896696538
SN - 2211-1247
VL - 6
SP - 625
EP - 632
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -