Differential Activities of Secreted Lymphotoxin-α3 and Membrane Lymphotoxin-α1β2 in Lymphotoxin-Induced Inflammation: Critical Role of TNF Receptor 1 Signaling

摘要: Lymphotoxin (LT, LTα, TNFβ) is a member of the immediate TNF family that also includes TNF-α and lymphotoxin-β (LTβ). LT produced by activated lymphocytes functions as either secreted homotrimer or membrane-associated heterotrimer transmembrane protein LTβ. Secreted LTα 3 can bind to two cell surface receptors, TNFR1 TNFR2, while membrane-bound 1 β 2 has been shown interact with distinct receptor, LTβR. induces inflammation at sites expression rat insulin promoter-driven lymphotoxin (RIPLT) transgene in pancreas kidney. To determine role various ligands their receptors LT-induced inflammation, mice deficient TNFR1, LTβ were crossed RIPLT-transgenic mice. Our results indicate LTα-induced dependent on interaction there no obvious for since its absence, quantitatively qualitatively similar seen wild type. However, absence accentuated infiltration kidney an increase proportion memory cells infiltrate. These data show crucial signaling via separate membrane form this inflammatory process.