Malt1 self-cleavage is critical for regulatory T cell homeostasis and anti-tumor immunity in mice

European Journal of Immunology
Mathijs BaensSimon Bornschein

Abstract

Mucosa-associated lymphoid tissue 1 (Malt1) regulates immune cell function by mediating the activation of nuclear factor κB (NF-κB) 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-κB activity. Until now, the functional distinction between Malt1 self-cleavage and its general protease function in regulating NF-κB 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-κB 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 prote...Continue Reading

References

Oct 3, 2002·Nature Reviews. Immunology·Qiutang Li, Inder M Verma
Jan 11, 2003·Science·Shohei HoriShimon Sakaguchi
Oct 25, 2003·Science·Astrid A Ruefli-BrasseVishva M Dixit
May 4, 2004·Nature Reviews. Immunology·Margot Thome
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Afonso R M AlmeidaAntonio A Freitas
Dec 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gaynor J BatesAlison H Banham
Feb 12, 2008·Nature Immunology·Fabien RebeaudMargot Thome
Jul 31, 2009·Blood·Girdhari Lal, Jonathan S Bromberg
Aug 6, 2010·Cold Spring Harbor Perspectives in Biology·Margot ThomeStephan Hailfinger
Aug 28, 2012·Nature Immunology·Dipayan RudraAlexander Y Rudensky
Jun 4, 2013·The Journal of Allergy and Clinical Immunology·Haifa H JabaraRaif S Geha
Nov 20, 2013·The Journal of Experimental Medicine·Inês F AmadoAntonio A Freitas
Dec 18, 2013·The Journal of Allergy and Clinical Immunology·Margaret L McKinnonStuart E Turvey
Jan 15, 2014·Current Opinion in Immunology·Hiroyoshi Nishikawa, Shimon Sakaguchi
Feb 1, 2014·Nature Reviews. Immunology·Adrian Liston, Daniel H D Gray
Aug 5, 2014·The Journal of Allergy and Clinical Immunology·Stuart E TurveyKlaus Warnatz
Sep 30, 2014·Nature Immunology·Andrew G LevineAlexander Y Rudensky
Jan 30, 2015·Journal of Clinical Immunology·Divya PunwaniJennifer M Puck
Sep 26, 2015·Cell Death and Differentiation·A BrüstleT W Mak
Mar 8, 2016·The Journal of Allergy and Clinical Immunology·Stéphanie Humblet-BaronAdrian Liston
Oct 21, 2016·Nature Immunology·Takatoshi ChinenAlexander Y Rudensky
Oct 13, 2017·European Journal of Immunology·Andrea CossarizzaJakob Zimmermann

❮ Previous
Next ❯

Citations

Apr 14, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Liqing ChengXin Lin
Oct 30, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kea MartinThomas Calzascia
Sep 15, 2018·Frontiers in Immunology·Mélanie Juilland, Margot Thome
Sep 3, 2019·Frontiers in Immunology·Annelies DemeyerRudi Beyaert
Oct 22, 2020·IScience·Annelies DemeyerRudi Beyaert
Mar 15, 2021·Current Opinion in Immunology·Henry Y Lu, Stuart E Turvey

❮ Previous
Next ❯

Methods Mentioned

BETA
PMA
protease assay
PCR
flow cytometry
FCS
Transfection
FACS

Software Mentioned

mcf
fastq
GraphPad Prism
FastQC
package DESeq2
HTSeq
Tophat2
R

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Related Papers

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Laura MeloniRudi Beyaert
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Linda M McAllister-LucasPeter C Lucas
© 2022 Meta ULC. All rights reserved