MALT1-Deficient Mice Develop Atopic-Like Dermatitis Upon Aging

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.

Defining the combinatorial space of PKC::CARD‐CC signal transduction nodes

“…The proteolytic activity of MALT1 was also found to be critical for certain cancers [16], which has stimulated an interest in MALT1 protease activity as a cancer therapy target as well. However, MALT1 inhibition may be a double‐edged sword as MALT1 deficiency in mice and humans has been linked with immunodeficiency as well as autoimmunity [17–25]. MALT1 also seems to be able to be activated independently of CBM‐complex formation, which is highlighted by its presence in organisms lacking BCL10 and CARD‐CC homologs [10,26] and by its activation by overexpression of TRAF6 or viral effector proteins [27,28].…”

Advances and novel developments in mechanisms of allergic inflammation

“…Because many of the substrates are involved in regulating inflammatory responses, the protease activity of MALT1 has emerged as a possible therapeutic target. Deregulated MALT1 activity has been associated with immunodeficiency, autoimmunity and cancer in mice and humans 31 . Genetically engineered mice expressing catalytically inactive MALT1, which still have a scaffold function, were shown to spontaneously develop autoimmunity due to a decrease in Treg cells 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 signalling. However, MALT1‐deficient mice develop atopic‐like dermatitis upon ageing, which is preceded by Th2 skewing, an increase in serum IgE, and a decrease in Treg and surface expression of the Treg functionality marker CTLA‐4 31 . In addition, MALT‐1 protease‐deficient mice display B‐cell hyperactivation to environmental antigens driving atopic disease 32 .…”

Evaluation of animal models of Crohn's disease with anal fistula (Review)

“…Mice, which have a strong reproductive capacity and a short reproductive cycle may be used to establish a variety of gene-modified mouse models and to spontaneously induce fistula-associated disease (28,29). However, due to the long disease cycle and low incidence rate, the practicability of this model is limited.…”