Asparaginyl Endopeptidase (Legumain) Supports Human Th1 Induction via Cathepsin L-Mediated Intracellular C3 Activation
FRONTIERS IN IMMUNOLOGY
Authors: Freeley, Simon; Cardone, John; Guenther, Sira C.; West, Erin E.; Reinheckel, Thomas; Watts, Colin; Kemper, Claudia; Kolev, Martin, V
Abstract
Autocrine activation of the complement receptors C3aR and CD46 by complement activation components C3a and C3b produced through C3 cleavage by the protease cathepsin L (CTSL) during T cell stimulation is a requirement for IFN-gamma production and Th1 induction in human CD4(+) T cells. Thus, lack of autocrine CD46 activation, such as in CD46-deficient patients, is associated with defective Th1 responses and recurrent infections. We have identified LGMN [the gene coding for legumain, also known as asparaginyl endopeptidase (AEP)] as one of the key genes induced by CD46 co-stimulation during human CD4(+) T cell activation. AEP processes and activates a range of proteins, among those alpha 1-thymosin and CTSL, which both drive intrinsically Th1 activity-but has so far not been described to be functionally active in human T cells. Here we found that pharmacological inhibition of AEP during activation of human CD4(+) T cells reduced CTSL activation and the CTSL-mediated generation of intracellular C3a. This translated into a specific reduction of IFN-gamma production without affecting cell proliferation or survival. In line with these findings, CD4(+) T cells isolated from Lgmn(-/-) mice also displayed a specific defect in IFN-gamma secretion and Th1 induction. Furthermore, we did not observe a role for AEP-driven autocrine alpha 1-thymosin activation in T cell-derived IFN-gamma production. These data suggest that AEP is an "upstream" activator of the CTSL-C3-IFN-gamma axis in human CD4(+) T cells and hence an important supporter of human Th1 induction.
A novel LaGa0.65Mg0.15Ni0.20O3-delta perovskite catalyst with high performance for the partial oxidation of methane to syngas
CATALYSIS TODAY
Authors: Meng, Bo; Zhang, Hongyu; Zhao, Zihang; Wang, Xiaobin; Jin, Yun; Liu, Shaomin
Abstract
A novel perovskite catalyst with the composition of LaGa0.65Mg0.15Ni0.20O3-delta (LGMN) is synthesized by the sol-gel combustion technique. The nanostructure catalyst has been examined for the partial oxidation of methane (POM) into syngas. A variety of characterizations including XRD, BET, SEM and TG-DTA were applied to determine the crystalline structure of the formed nanosized particles. The syngas selectivity over the catalyst may reach up to 100% with the methane conversions larger than 81% at 900 degrees C and 55 mL min(-1) g(-1) feed velocity. XRD and thermal analysis reveals that the LGMN powder has maintained the perovskite structure very well after 210 h POM reaction signaling its high chemical stability. (C) 2015 Elsevier B.V. All rights reserved.