Abstract
MALT1 plays an important role in innate and adaptive immune signaling by acting as a scaffold protein that mediates NF-κB signaling. In addition, MALT1 is a cysteine protease that further fine tunes proinflammatory signaling by cleaving specific substrates. Deregulated MALT1 activity has been associated with immunodeficiency, autoimmunity, and cancer in mice and humans. Genetically engineered mice expressing catalytically inactive MALT1, still exerting its scaffold function, were previously shown to spontaneously develop autoimmunity due to a decrease in Tregs associated with increased effector T cell activation. In contrast, complete absence of MALT1 does not lead to autoimmunity, which has been explained by the impaired effector T cell activation due to the absence of MALT1-mediated signaling. However, here we report that MALT1-deficient mice develop atopic-like dermatitis upon aging, which is preceded by Th2 skewing, an increase in serum IgE, and a decrease in Treg frequency and surface expression of the Treg functionality marker CTLA-4.
Highlights
MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1) is an intracellular signaling protein that plays an important role in several cell types, including lymphoid and myeloid cells as well as non-hematopoietic cells [1]
MALT1 is best known for its role as a scaffold protein in T cell receptor (TCR)- and B cell receptor (BCR)-induced nuclear factor-κB (NF-κB) signaling, leading to the activation and proliferation of T and B cells, respectively [2, 3]
We report that aging Malt1-KO mice suffer from atopic-like dermatitis accompanied by elevated serum cytokine levels and preceded by Th2 skewing and elevated serum IgE levels
Summary
MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1) is an intracellular signaling protein that plays an important role in several cell types, including lymphoid and myeloid cells as well as non-hematopoietic cells [1]. TCR or BCR stimulation, as well as oncogenic mutations in specific signaling proteins, leads to the formation of a so-called CBM signaling complex, consisting of CARD11 ( known as CARMA1), BCL10 and MALT1 [8, 14,15,16,17,18]. In this complex, MALT1 acts as an adaptor to recruit the E3 ubiquitin ligase TRAF6, whose activity facilitates the recruitment and activation of downstream NF-κB signaling proteins [19,20,21]. The importance of the CBM complex is illustrated by the impaired TCR-induced NF-κB activation in T cells isolated from Card11-, Bcl10-, and Malt1-knock-out (KO) mice, respectively [2, 3, 22, 23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
