Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity.

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Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_9401281135B4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity.
Périodique
EMBO Journal
Auteur(s)
Jaworski M., Marsland B.J., Gehrig J., Held W., Favre S., Luther S.A., Perroud M., Golshayan D., Gaide O., Thome M.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
2014
Volume
33
Numéro
23
Pages
2765-2781
Langue
anglais
Résumé
The protease activity of the paracaspase Malt1 has recently gained interest as a drug target for immunomodulation and the treatment of diffuse large B-cell lymphomas. To address the consequences of Malt1 protease inactivation on the immune response in vivo, we generated knock-in mice expressing a catalytically inactive C472A mutant of Malt1 that conserves its scaffold function. Like Malt1-deficient mice, knock-in mice had strong defects in the activation of lymphocytes, NK and dendritic cells, and the development of B1 and marginal zone B cells and were completely protected against the induction of autoimmune encephalomyelitis. Malt1 inactivation also protected the mice from experimental induction of colitis. However, Malt1 knock-in mice but not Malt1-deficient mice spontaneously developed signs of autoimmune gastritis that correlated with an absence of Treg cells, an accumulation of T cells with an activated phenotype and high serum levels of IgE and IgG1. Thus, removal of the enzymatic activity of Malt1 efficiently dampens the immune response, but favors autoimmunity through impaired Treg development, which could be relevant for therapeutic Malt1-targeting strategies.
Pubmed
Web of science
Création de la notice
02/01/2015 10:33
Dernière modification de la notice
03/03/2018 19:36
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