TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis

摘要: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases psoriasis, whereas no data available on involvement sarcoidosis, multisystemic granulomatous disease where deregulated helper (Th)1/Th17 response takes place. In this study, by flow cytometry, real-time PCR, confocal microscopy immunohistochemistry analyses, TL1A DR3 were investigated pulmonary cells peripheral blood 43 patients affected sarcoidosis different phases (29 with active 14 inactive form) 8 control subjects. Our results demonstrated significant higher expression, both at protein mRNA levels, alveolar macrophages as compared form controls. was strongly more expressed lung than blood, i.e., site involved organ. Additionally, zymography assays showed that is able increase production matrix metalloproteinase 9 sarcoid characterized, disease, reduced levels tissue inhibitor (TIMP)-1. These suggest TL1A/DR3 interactions part extended complex network characterizes during phase may contribute pathogenesis progression disease.