Transmembrane tumor necrosis factor is a potent inducer of colitis even in the absence of its secreted form

Gastroenterology
N CorazzaChristoph Mueller

Abstract

Tumor necrosis factor (TNF) is cleaved proteolytically from a 26-kilodalton transmembrane precursor protein into secreted 17-kilodalton monomers. Transmembrane (tm) and secreted trimeric TNF are biologically active and may mediate distinct activities. We assessed the consequences of a complete inhibition of TNF processing on the course of colitis in recombination activating gene (RAG)2 -/- mice on transfer of CD4 CD45RB hi T cells. TNF -/- mice, transgenic for a noncleavable mutant TNF gene, were used as donors of CD4 T cells, and, on a RAG2 -/- background, also as recipients. Kinetics of disease development were compared in the absence of TNF, in the absence of secreted TNF, and in the presence of secreted and tmTNF. The analysis at the end of the observation period included the histopathologic assessment of the intestine and the localization of TNF and interferon gamma (IFNgamma)-expressing cells. The complete prevention of TNF secretion in tmTNF transgenic RAG2 -/- mice neither prevented nor delayed disease induction by transferred transgenic for a noncleavable transmembrane mutant of mouse TNF (tmTNF tg) CD4 CD45RB hi T cells. tmTNF expression by transferred CD4 T cells, however, was not required for disease induction becau...Continue Reading

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Citations

Aug 12, 2006·Multiple Sclerosis : Clinical and Laboratory Research·J PlumbM N Woodroofe
Aug 15, 2009·European Journal of Immunology·Stefan MüllerChristoph Mueller
May 5, 2010·The Journal of Experimental Medicine·Mario NotiThomas Brunner
Apr 19, 2019·International Journal of Molecular Sciences·Barbara RuderChristoph Becker
Sep 29, 2020·Frontiers in Medicine·Raja AtreyaBritta Siegmund
Aug 2, 2007·Expert Opinion on Biological Therapy·Herbert TilgArthur Kaser
Aug 3, 2019·Expert Opinion on Biological Therapy·Irene MarafiniGiovanni Monteleone
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Jan 13, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ellen C Ebert
Nov 30, 2016·World Journal of Gastroenterology : WJG·Ulrike BillmeierRaja Atreya

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