Death Receptor 3 Promotes Chemokine-Directed Leukocyte Recruitment in Acute Resolving Inflammation and Is Essential for Pathological Development of Mesothelial Fibrosis in Chronic Disease
| Autor: | Edward Chung Yern Wang, Ravinder K. Singh, Gareth W. Jones, Anwen Sian Williams, Philip R. Taylor, Jason Peter Twohig, William Victor Perks, Ian R. Humphreys, Simon Arnett Jones |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Male Tumor Necrosis Factor Ligand Superfamily Member 15 Muromegalovirus endocrine system diseases T-Lymphocytes Short Communication Biology CCL7 Epithelium Pathology and Forensic Medicine Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine immune system diseases Leukocytes Staphylococcus epidermidis CXCL10 Animals Humans CXCL13 skin and connective tissue diseases Receptors Tumor Necrosis Factor Member 25 Inflammation Innate lymphoid cell Connective tissue stroma R1 Fibrosis CXCL1 Mice Inbred C57BL 030104 developmental biology Immunology Acute Disease Chronic Disease Tumor necrosis factor alpha Female Chemokines Peritoneum 030215 immunology Signal Transduction |
| Zdroj: | The American journal of pathology. 186(11) |
| ISSN: | 1525-2191 0002-9440 |
| Popis: | Death receptor 3 (DR3; TNFRSF25) and its tumor necrosis factor–like ligand TL1A (TNFSF15) control several processes in inflammatory diseases through the expansion of effector T cells and the induction of proinflammatory cytokines from myeloid and innate lymphoid cells. Using wild-type (DR3 +/+ ) and DR3-knockout (DR3 −/− ) mice, we show that the DR3/TL1A pathway triggers the release of multiple chemokines after acute peritoneal inflammation initiated by a single application of Staphylococcus epidermidis supernatant, correlating with the infiltration of multiple leukocyte subsets. In contrast, leukocyte infiltration was not DR3 dependent after viral challenge with murine cytomegalovirus. DR3 expression was recorded on connective tissue stroma, which provided DR3-dependent release of chemokine (C-C motif) ligand (CCL) 2, CCL7, CXCL1, and CXCL13. CCL3, CCL4, and CXCL10 production was also DR3 dependent, but quantitative RT-PCR showed that their derivation was not stromal. In vitro cultures identified resident macrophages as a DR3-dependent source of CCL3. Whether DR3 signaling could contribute to a related peritoneal pathology was then tested using multiple applications of S. epidermidis supernatant, the repetitive inflammatory episodes of which lead to peritoneal membrane thickening and collagen deposition. Unlike their DR3 +/+ counterparts, DR3 −/− mice did not develop fibrosis of the mesothelial layer. Thus, this work describes both a novel function and essential requirement for the DR3/TL1A pathway in acute, resolving, and chronic inflammation in the peritoneal cavity. |
| Databáze: | OpenAIRE |
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