The protease MALT1 is a key regulator of NF-κB signaling and a novel therapeutic target in autoimmunity and cancer. Initial enthusiasm supported by preclinical results with MALT1 inhibitors was tempered by studies showing that germline MALT1 protease inactivation in mice results in reduced regulatory T cells and lethal multi-organ inflammation due to expansion of IFN-γ-producing T cells. However, we show that long-term MALT1 inactivation, starting in adulthood, is not associated with severe systemic inflammation, despite reduced regulatory T cells. In contrast, IL-2-, TNF-, and IFN-γ-producing CD4 T cells were strongly reduced. Limited formation of tertiary lymphoid structures was detectable in lungs and stomach, which did not affect overall health. Our data illustrate that MALT1 inhibition in prenatal or adult life has a different outcome and that long-term MALT1 inhibition in adulthood is not associated with severe side effects.
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http://dx.doi.org/10.1016/j.isci.2020.101557 | DOI Listing |
Sci Rep
February 2024
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
The objective of this study was to clarify the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma with additional copies of MALT1. In this multicenter retrospective study, we enrolled 145 patients with gastric MALT lymphoma who underwent fluorescence in situ hybridization (FISH) analysis to detect t(11;18) translocation. The patient cohort was divided into three groups: Group A (n = 87), comprising individuals devoid of the t(11;18) translocation or extra MALT1 copies; Group B (n = 27), encompassing patients characterized by the presence of the t(11;18) translocation; and Group C (n = 31), including patients with extra MALT1 copies.
View Article and Find Full Text PDFBr J Haematol
January 2024
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Marginal zone lymphoma (MZL) is the most common indolent lymphoma primarily arising in the central nervous system (CNS). To date, 207 cases of primary CNS MZL (PCNSMZL) were published, mostly as single case reports or small case series. It most commonly presents as extra-axial dural-based masses, more frequently in middle-aged women, displaying an insidious onset, with a long history of symptoms preceding the diagnosis.
View Article and Find Full Text PDFBiochem Pharmacol
December 2023
Biomedical Research Service, John D. Dingell VA Medical Center, and Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address:
It is widely accepted that pancreatic islet β-cell failure and the onset of type 2 diabetes (T2DM) constitute an intricate interplay between the genetic expression of the disease and a host of intracellular events including increased metabolic (oxidative, endoplasmic reticulum) stress under the duress of glucolipotoxicity. Emerging evidence implicates unique roles for Caspase Recruitment Domain containing protein 9 (CARD9) in the onset of metabolic diseases, including obesity and insulin resistance. Mechanistically, CARD9 has been implicated in the regulation of p38MAPK and NFkB signaling pathways culminating in cellular dysfunction.
View Article and Find Full Text PDFIntern Med
June 2024
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
A 38-year-old Japanese man was diagnosed with extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma). Fluorescence in situ hybridization analysis revealed the absence of t (11;18) (q21;q21) translocation but the presence of extra copies of MALT1, indicating tetrasomy 18. Helicobacter pylori eradication led to complete remission (CR).
View Article and Find Full Text PDFACS Chem Neurosci
September 2023
Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has been confirmed to contribute to brain injury in ischemic stroke via promoting excitotoxicity and necroptosis. Telaprevir, a hepatitis C virus protease inhibitor, is predicted to be a potential MALT1 inhibitor. Here, we showed that telaprevir protected against cerebral ischemic injury via inhibiting MALT1, thereby preventing glutamate receptor ionotropic NMDA 2B (GluN2B) activation, limiting calcium overload, and suppressing necroptosis.
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