| First Author | Baens M | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 10 | Pages | 1728-1738 |
| PubMed ID | 30025160 | Mgi Jnum | J:266646 |
| Mgi Id | MGI:6201511 | Doi | 10.1002/eji.201847597 |
| Citation | Baens M, et al. (2018) Malt1 self-cleavage is critical for regulatory T cell homeostasis and anti-tumor immunity in mice. Eur J Immunol 48(10):1728-1738 |
| abstractText | Mucosa-associated lymphoid tissue 1 (Malt1) regulates immune cell function by mediating the activation of nuclear factor kappaB (NF-kappaB) signaling through both its adaptor and proteolytic function. Malt1 is also a target of its own protease activity and this self-cleavage further contributes to NF-kappaB activity. Until now, the functional distinction between Malt1 self-cleavage and its general protease function in regulating NF-kappaB signaling and immune activation remained unclear. Here we demonstrate, using a new mouse model, the importance of Malt1 self-cleavage in regulating expression of NF-kappaB target genes and subsequent T cell activation. Significantly, we further establish that Treg homeostasis is critically linked to Malt1 function via a Treg intrinsic and extrinsic mechanism. TCR-mediated Malt1 proteolytic activity and self-cleavage was found to drive Il2 expression in conventional CD4(+) T cells, thereby regulating Il2 availability for Treg homeostasis. Remarkably, the loss of Malt1-mediated self-cleavage alone was sufficient to cause a significant Treg deficit resulting in increased anti-tumor immune reactivity without associated autoimmunity complications. These results establish for the first time that inhibition of MALT1 proteolytic activity could be a viable therapeutic strategy to augment anti-tumor immunity. |
