Bornancin, Frederic, Renner, Florian, Touil, Ratiba, Kolb, Yeter, Touil, Ismahane, Rush, James, Smith, Paul, Bigaud, Marc, Zamurovic Ribrioux, Natasa, Junker Walker, Ursula, Burkhart, Christoph, Dawson King, Janet, Regnier, Catherine, Niwa, Satoru, Katopodis, Andreas, Nuesslein-Hildesheim, Barbara, Weckbecker, Gisbert, Zenke, Gerhard, Kinzel, Bernd, Traggiai, Elisabetta, Brenner, Dirk, Brüstle, Anne, St Paul, Michael, McCoy, Kathy D., Rolink, Antonius, Mak, Tak W, Ohashi, Pamela S, Patel, Dhavalkumar and Calzascia, Thomas (2015) Deficiency in MALT1 paracaspase activity promotes multi-organ inflammation. Journal of Immunology, 194 (8). pp. 3723-3734. ISSN 1550-6606

Abstract

The paracaspase MALT1 plays an important role in signaling pathways leading to NF-kB activation. To investigate the contribution of its proteolytic activity to overall pathway regulation we generated MALT1 protease-deficient mice (Malt1PD/PD) and compared them to MALT1 KO animals (Malt1-/-). Malt1PD/PD mice displayed defects in multiple cell types including Treg, IL10-producing B cells and mature T and B cells. Immune defects were more pronounced in Malt1-/- animals. Both mouse lines showed abrogated B cell responses upon immunization and were protected in a Th17-dependent EAE model. Surprisingly, Malt1PD/PD animals developed a multi-organ inflammation characterized by Th2-type responses and enhanced IgG1 and IgE levels which was prevented by reconstitution with WT Treg. These data uncover a previously unappreciated key function of MALT1 protease activity in immune homeostasis and its relevance in human health and disease.

Item Type:	Article
Keywords:	MALT1, multi-organ inflammation
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/22241