Human NACHT, LRR, and PYD domain–containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase

Liu, Xiao; Pichulik, Tica; Wolz, Olaf Oliver; Dang, Truong Minh; Stutz, Andrea; Dillen, Carly; Garcia, Magno Delmiro; Kraus, Herbert; Dickhöfer, Sabine; Daiber, Ellen; Münzenmayer, Lisa; Wahl, Silke; Rieber, Nikolaus; Kümmerle-Deschner, Jasmin; Yazdi, Amir S.; Franz‐Wachtel, Mirita; Maček, Boris; Radsak, Markus P.; Vogel, Sebastian; Schulte, Berit; Walz, Juliane S.; Hartl, Dominik; Latz, Eicke; Stilgenbauer, Stephan; Grimbacher, Bodo; Miller, Lloyd S.; Brunner, Cornelia; Wolz, Christiane; Weber, Alexander N.R.

doi:10.1016/j.jaci.2017.01.017

Cited by 108 publications

(134 citation statements)

References 52 publications

(76 reference statements)

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“…Previous studies of NLRP3 inflammasome regulation by BTK, most notably those conducted by Liu et al (10) and Ito et al (11) using BTK-deficient cells, have led to the conclusion that BTK enhances NLRP3 inflammasome activity. However, these studies were based in part on comparisons of inflammasome responses of WT and BTK-deficient cells after stimulation with low doses of LPS and therefore overlooked the fact that deficient NLRP3 inflammasome responses in BTK-KO cells, presumably indicative of deficient BTK-enhancing activity, could be due to defects in TLR4 activation (12).…”

Section: Introductionmentioning

confidence: 99%

Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β–mediated colitis

Mao

Kitani

Hiejima

et al. 2020

Journal of Clinical Investigation

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Section: Introductionmentioning

confidence: 99%

Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β–mediated colitis

Mao

Kitani

Hiejima

et al. 2020

Journal of Clinical Investigation

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“…e function of NOD prompts NLR molecular aggregation to change its configuration [17]. e N-terminal is the effector domain, mainly composed of caspase recruitment domain (CARD), pyrin domain (PYD), or baculovirus inhibitor of apoptosis protein repeat domain (BIR), which mediates the homologous protein interaction to transmit signals downstream [18]. According to the structural characteristics of the effect domain, several subfamilies can be further divided, including NLRA, NLRB, NLRC, and NLRP [19].…”

Section: Structure Of Nlrp3mentioning

confidence: 99%

NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis

Yang

Yin

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Atherosclerosis (AS) is a complex and chronic inflammatory disease that occurs in multiple systems of the human body. It is an important pathological basis for a variety of diseases and a serious threat to human health. So far, many theories have been formed to explain the pathogenesis of atherosclerosis, among which “inflammation theory” has gradually become a research focus. This theory presents that inflammatory response runs through the whole progress of AS, inflammatory cells play as the main executors of AS, and inflammatory mediators are the key molecules of AS. In the inflammatory process of atherosclerosis, the role of NLRP3 in the atherosclerosis has gradually got the attention of researchers. NLRP3 is a kind of signal-transductional pattern recognition receptors (PRRs). After recognizing and binding to the damage factors, NLRP3 inflammasome will be assembled to activate IL-1β and caspase-1 pathways, resulting in promoting the inflammation process of AS, reducing the stability of the plaques, and finally increasing the incidence of adverse cardiovascular events. Taken above, the article will review the potential benefits of drugs targeting the NLRP3 inflammasome in the therapy of AS.

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“…In Borrelia hermsii ‐infected mice, Btk‐deficient mice exhibit weaker T cell‐independent pathogen‐specific IgM responses and higher‐level persistent bacteraemia than WT mice . In Staphylococcus aureus ‐infected mice, Btk inhibition negatively regulates IL‐1β‐dependent bacterium clearance through impairing NLRP3 inflammasome activation and blocking IL‐1β release . In macrophages derived from patients with chronic lymphocytic leukaemia (CLL), the Btk inhibitor ibrutinib impairs the secretion of TNF‐α and affects polarization towards the pro‐inflammatory profile against irradiated Mycobacterium tuberculosis .…”

Section: Btk and Pathogenic Microorganism Infectionsmentioning

confidence: 99%

“…43 In Staphylococcus aureus-infected mice, Btk inhibition negatively regulates IL-1β-dependent bacterium clearance through impairing NLRP3 inflammasome activation and blocking IL-1β release. 25 In macrophages derived from patients with chronic lymphocytic leu-…”

Section: Effect Of Btk In Bacterial Infectionsmentioning

confidence: 99%

Effects of BTK signalling in pathogenic microorganism infections

Zhou

Guo

et al. 2019

J Cellular Molecular Medi

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As a cytoplasmic protein tyrosine kinase, Bruton's tyrosine kinase (Btk) is widely considered as a vital kinase in many aspects of different physiologic processes. It is engaged in many important signalling pathways related to the immune response, such as the B cell receptor pathway, pattern‐recognition receptor pathway, and triggering receptor expressed on myeloid cell pathway. Recent studies have increasingly focused on the important role of Btk in various inflammatory diseases, which are related to Btk expression in myeloid innate immune cells, such as macrophages, dendritic cells and neutrophils. Although some investigations have explored the role of Btk in microbial infections, many aspects remain elusive, and some of the results are opposite and controversial. Considering the complicated and multiple roles of Btk in the immune system, we summarized the engagement of Btk signalling in various pathogenic microorganism infections, the possible mechanisms involved and its therapeutic potential in the control of infectious diseases.

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Human NACHT, LRR, and PYD domain–containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase

Abstract: Our data suggest that XLA might result in part from genetic inflammasome deficiency and that NLRP3 inflammasome-linked inflammation could potentially be targeted pharmacologically through BTK.

Cited by 108 publications

References 52 publications

Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β–mediated colitis

Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β–mediated colitis

NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis

Effects of BTK signalling in pathogenic microorganism infections

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