Malt1 inactivation attenuates experimental colitis through the regulation of Th17 and Th1/17 cells

Nakamura, Yoshiki; Igaki, Keiko; Komoike, Yusaku; Yokoyama, Kazumasa; Tsuchimori, Noboru

doi:10.1007/s00011-018-1207-y

Cited by 13 publications

(32 citation statements)

References 25 publications

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“…As a crucial regulator, MALT1 activates nuclear factor‐kappa‐B (NF‐κB) signaling pathway to induce signaling‐mediated macrophage activation and further promotes the inflammatory response 19,20 . In addition, MALT1 is involved in inducing and promoting the differentiation of T‐helper 1 (Th1) and T‐helper 17 (Th17) cells, which aggravates many inflammatory and autoimmune diseases 21‐24 . Besides, considering that RA is a chronic autoimmune disease, we assumed that MALT1 might serve as a novel biomarker for RA.…”

Section: Introductionmentioning

confidence: 99%

Blood MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in rheumatoid arthritis patients; meanwhile, MALT1 decline during therapy relates to treatment outcome

Zhuang

Chen

Fang

et al. 2021

Clinical Laboratory Analysis

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Objective Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) participates in inflammatory and autoimmune diseases via activating various signaling pathways and promoting the differentiation of T‐helper (Th) 1 and Th17 cells; however, it is rarely reported in rheumatoid arthritis (RA). This study aimed to assess the correlation of MALT1 with Th1 and Th17 cells and evaluate its potential as a biomarker for evaluating disease activity and treatment outcomes in RA patients. Methods This study enrolled 139 RA patients and 45 health controls (HCs); then, blood MALT1, Th1, and Th17 cells were determined. For RA patients only, blood MALT1 at week (W) 6 and W12 after treatment was also detected. Additionally, clinical response and remission of RA patients were assessed at W12. Results MALT1 (p < 0.001), Th1 (p = 0.011), and Th17 (p < 0.001) cells were all increased in RA patients than HCs; meanwhile, increased MALT1 was associated with elevated Th1 (p = 0.003) and Th17 (p < 0.001) cells in RA patients. Besides, MALT1, Th1, and Th17 cells were positively correlated with parts of disease activity indexes in RA patients (all p < 0.050). In addition, MALT1 was gradually declined from W0 to W12 (p < 0.001) in RA patients. Specifically, MALT1 at W6 and W12 was lower in response patients than no response patients (both p < 0.010), also in remission patients than no remission patients (both p < 0.050). Conclusion MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in RA patients; meanwhile, the decline of MALT1 expression can partly reflect RA treatment response and remission.

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Section: Introductionmentioning

confidence: 99%

Blood MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in rheumatoid arthritis patients; meanwhile, MALT1 decline during therapy relates to treatment outcome

Zhuang

Chen

Fang

et al. 2021

Clinical Laboratory Analysis

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“…Previous studies indicate that MALT1 regulates CD4 + T‐cell differentiation into Th1 and 17 cells, and their effector response based on in vitro study 12 . Meanwhile, in vivo, the MALT1 deficiency colitis mouse model displayed a reduction of the Th17 cell amount and IL‐17A (Th17 cell secreted cytokines) 11 . Furthermore, MALT1 deficiency resulted in a declined T‐cell proliferation as well as unbalanced regulatory T‐cell and effector T‐cell amount, which further led to inflammation of multiorgan 13 .…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore, apart from that, MALT1 enhances vascular inflammation and endothelial barrier disruption in several studies 14‐17 . Because MALT1 may enhance inflammatory cytokine production in endothelial cells and induce endothelial dysfunction, and these physiological changes indicate further atherosclerosis, thrombosis formation, and AIS occurrence and also MALT1 regulates Th cell differentiation and their related inflammatory cytokine excretion; therefore, we hypothesized that MALT1 measurement might play a pivotal role for AIS management 10‐12,18‐20 . In our preliminary study with a relatively small sample size, we discovered that MALT1 was increased in AIS patients compared with controls.…”

Section: Introductionmentioning

confidence: 85%

“…Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key mediator in the nuclear factor (NF)‐κB signaling pathway which is involved in lymphocyte activation, proliferation, and survival via its link to different receptors 7‐9 . Meanwhile, previous studies disclose that MALT1 regulates a cluster of differentiation 4‐positive (CD4 + ) T‐cell differentiation into T helper type 1 (Th1) cells and Th17 cells 10‐13 . Furthermore, apart from that, MALT1 enhances vascular inflammation and endothelial barrier disruption in several studies 14‐17 .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] Meanwhile, previous studies disclose that MALT1 regulates a cluster of differentiation 4-positive (CD4 + ) T-cell differentiation into T helper type 1 (Th1) cells and Th17 cells. [10][11][12][13] Furthermore, apart from that, MALT1 enhances vascular inflammation and endothelial barrier disruption in several studies. [14][15][16][17] Because MALT1 may enhance inflammatory cytokine production in endothelial cells and induce endothelial dysfunction, and these physiological changes indicate further atherosclerosis, thrombosis formation, and AIS occurrence and also MALT1 regulates Th cell differentiation and their related inflammatory cytokine excretion; therefore, we hypothesized that MALT1 measurement might play a pivotal role for AIS management.…”

Section: Introductionmentioning

confidence: 99%

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MALT1 positively correlates with Th1 cells, Th17 cells, and their secreted cytokines and also relates to disease risk, severity, and prognosis of acute ischemic stroke

Chen

Zhang

Ling

et al. 2021

Clinical Laboratory Analysis

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Background This study aimed to explore the association of mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) with acute ischemic stroke (AIS) risk and also to explore its association with T helper type 1 (Th1) cells, Th17 cells, disease severity, and prognosis in AIS patients. Methods One hundred twenty first‐episode AIS patients and 120 non‐AIS patients with high‐stroke‐risk factors (as controls) were recruited. Besides, in the cluster of differentiation 4‐positive (CD4+) T cells, the MALT1 gene expression was detected by reverse transcription quantitative polymerase chain reaction; meanwhile, Th1 and Th17 were detected by flow cytometry. Moreover, serum interferon (IFN)‐γ and interleukin (IL)‐17 were determined by enzyme‐linked immunosorbent assay. Results MALT1 expression was increased in AIS patients compared with controls and also it could differentiate AIS patients from controls, with an area under curve of 0.905 (95% confidence interval: 0.869–0.941). In AIS patients, MALT1 positively correlated with Th1 cells, Th17 cells, IFN‐γ, and IL‐17. Besides, MALT1 positively correlated with the National Institutes of Health Stroke Scale score. Furthermore, the Kaplan‐Meier curve and univariate Cox's regression analyses showed no correlation of MALT1 high expression with recurrence‐free survival (RFS) in AIS patients, although after adjustment using multivariant Cox's regression, high MALT1 expression independently correlated with worse RFS in AIS patients. Conclusion MALT1 expression is increased and positively correlates with disease severity, Th1 cells, and Th17 cells, whose high expression severs as an independent risk factor for worse RFS in AIS patients.

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Chemical Probes for Profiling of MALT1 Protease Activity

Verhelst,

Prothiwa

2023

ChemBioChem

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The paracaspase MALT1 is a key regulator of the human immune response. It is implicated in a variety of human diseases. For example, deregulated protease activity drives the survival of malignant lymphomas and is involved in the pathophysiology of autoimmune/inflammatory diseases. Thus, MALT1 has attracted attention as promising drug target. Although many MALT1 inhibitors have been identified, molecular tools to study MALT1 activity, target engagement and inhibition in complex biological samples, such as living cells and patient material, are still scarce. Such tools are valuable to validate MALT1 as a drug target in vivo and to assess yet unknown biological roles of MALT1. In this review, we discuss the recent literature on the development and biological application of molecular tools to study MALT1 activity and inhibition.

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Malt1 inactivation attenuates experimental colitis through the regulation of Th17 and Th1/17 cells

Cited by 13 publications

References 25 publications

Blood MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in rheumatoid arthritis patients; meanwhile, MALT1 decline during therapy relates to treatment outcome

Blood MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in rheumatoid arthritis patients; meanwhile, MALT1 decline during therapy relates to treatment outcome

MALT1 positively correlates with Th1 cells, Th17 cells, and their secreted cytokines and also relates to disease risk, severity, and prognosis of acute ischemic stroke

Chemical Probes for Profiling of MALT1 Protease Activity

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