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Deficiency in MALT1 paracaspase activity promotes multi-organ inflammation

Bornancin, Frederic and Renner, Florian and Touil, Ratiba and Kolb, Yeter and Touil, Ismahane and Rush, James and Smith, Paul and Bigaud, Marc and Zamurovic Ribrioux, Natasa and Junker Walker, Ursula and Burkhart, Christoph and Dawson King, Janet and Regnier, Catherine and Niwa, Satoru and Katopodis, Andreas and Nuesslein-Hildesheim, Barbara and Weckbecker, Gisbert and Zenke, Gerhard and Kinzel, Bernd and Traggiai, Elisabetta and Brenner, Dirk and Brüstle, Anne and St Paul, Michael and McCoy, Kathy D. and Rolink, Antonius and Mak, Tak W and Ohashi, Pamela S and 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

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