Death Receptor 3 promotes chemokine directed leukocyte recruitment in acute resolving inflammation and is essential for pathological development of mesothelial fibrosis in chronic disease

摘要: 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 induction proinflammatory cytokines from myeloid innate lymphoid cells. Using wild-type (DR3 +/+ ) DR3-knockout −/− mice, we show that DR3/TL1A pathway triggers release multiple chemokines after acute peritoneal inflammation initiated by a single application Staphylococcus epidermidis supernatant, correlating with infiltration leukocyte subsets. In contrast, was not DR3 dependent viral challenge murine cytomegalovirus. expression recorded on connective tissue stroma, which provided DR3-dependent chemokine (C-C motif) (CCL) 2, CCL7, CXCL1, CXCL13. CCL3, CCL4, CXCL10 production also dependent, but quantitative RT-PCR showed their derivation stromal. In vitro cultures identified resident macrophages as source CCL3. Whether signaling could contribute to related pathology then tested using applications S. repetitive episodes lead membrane thickening collagen deposition. Unlike counterparts, mice did develop fibrosis mesothelial layer. Thus, this work describes both novel function essential requirement for acute, resolving, chronic cavity.