TRAIL suppresses gut inflammation and inhibits colitogeic T-cell activation in experimental colitis via an apoptosis-independent pathway
Journal
Mucosal Immunology
Journal Volume
12
Journal Issue
4
Pages
980-989
Date Issued
2019
Author(s)
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell apoptosis by transducing apoptosis signals. Recently, accumulating evidence demonstrated that TRAIL regulates autoimmune inflammation and immune cell homeostasis in several autoimmune animal models, suggesting a novel immunoregulatory role of TRAIL in autoimmune diseases. However, the impact of TRAIL in inflammatory bowel disease is yet undefined. This study is to address the therapeutic effects and immunoregulatory role of TRAIL in autoimmune gut inflammation. We demonstrated herein that TRAIL significantly suppressed gut inflammation and reduced the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis model. Suppression of gut inflammation was not due to induction of apoptosis in colonic T cells, dendritic cells, or epithelium cells by TRAIL. In contrast, TRAIL directly inhibited activation of colitogenic T cells and development of gut inflammation in an adoptive transfer-induced colitis model. The anti-inflammatory effects of TRAIL on colitis were abolished when T cells from TRAIL receptor (TRAIL-R) knockout mice were adoptively transferred, suggesting that TRAIL regulates autoreactive colitogenic T-cell activation in the development of gut inflammation. Our results demonstrate that TRAIL effectively inhibited colonic T-cell activation and suppressed autoimmune colitis, suggesting a potential therapeutic application of TRAIL in human inflammatory bowel disease. ? 2019, The Author(s).
SDGs
Other Subjects
complement component C5a; CXCL9 chemokine; gamma interferon; interleukin 16; interleukin 17; interleukin 1alpha; interleukin 33; RANTES; recombinant tumor necrosis factor related apoptosis inducing ligand; stromal cell derived factor 1; tumor necrosis factor; tumor necrosis factor related apoptosis inducing ligand; tumor necrosis factor related apoptosis inducing ligand receptor; autacoid; cytokine; dextran sulfate; tumor necrosis factor related apoptosis inducing ligand; adoptive transfer-induced colitis; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; apoptosis; Article; controlled study; cytokine production; dendritic cell; dextran sulfate sodium-induced colitis; disease severity; enteritis; epithelium cell; experimental colitis; female; immunoregulation; knockout mouse; mouse; nonhuman; priority journal; protein protein interaction; T lymphocyte; T lymphocyte activation; animal; apoptosis; autoimmunity; colitis; disease model; human; immunology; intestine mucosa; lymphocyte activation; metabolism; pathology; signal transduction; Animals; Apoptosis; Autoimmunity; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Humans; Inflammation Mediators; Intestinal Mucosa; Lymphocyte Activation; Mice; Mice, Knockout; Signal Transduction; T-Lymphocytes; TNF-Related Apoptosis-Inducing Ligand
Publisher
Nature Publishing Group
Type
journal article