21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The latest breakthrough on NLRP6 inflammasome

      review-article
      , , ,
      Precision Clinical Medicine
      Oxford University Press
      NLRP6, inflammasome, phase separation, human disease

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          NLRP6, a Nod-like receptor family member, has been shown to affect intestinal homeostasis and microbial colonization through organizing a huge protein complex called inflammasome. NLRP6 inflammasome promotes the cleavage and secretion of inflammatory cytokines or the cleavage of pore-forming Gasdermin D to initiate the inflammatory cell death called pyroptosis, which plays important roles in responding to pathogen invasion. However, questions about the ligand(s) that trigger NLRP6 inflammasome activation, or the mechanisms that how a ligand triggers NLRP6 inflammasome assembly, are emerging. In this mini-review, we summarize the current understandings of ligand recognition of NLRP6, the role of liquid-liquid phase separation in NLRP6 inflammasome assembly, and potential links with human health and diseases.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: found
          • Article: not found

          Protein Phase Separation: A New Phase in Cell Biology

          Cellular compartments and organelles organize biological matter. Most well-known organelles are separated by a membrane boundary from their surrounding milieu. There are also many so-called membraneless organelles and recent studies suggest that these organelles, which are supramolecular assemblies of proteins and RNA molecules, form via protein phase separation. Recent discoveries have shed light on the molecular properties, formation, regulation, and function of membraneless organelles. A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pathogen recognition and inflammatory signaling in innate immune defenses.

            The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling.

              Host-microbiome co-evolution drives homeostasis and disease susceptibility, yet regulatory principles governing the integrated intestinal host-commensal microenvironment remain obscure. While inflammasome signaling participates in these interactions, its activators and microbiome-modulating mechanisms are unknown. Here, we demonstrate that the microbiota-associated metabolites taurine, histamine, and spermine shape the host-microbiome interface by co-modulating NLRP6 inflammasome signaling, epithelial IL-18 secretion, and downstream anti-microbial peptide (AMP) profiles. Distortion of this balanced AMP landscape by inflammasome deficiency drives dysbiosis development. Upon fecal transfer, colitis-inducing microbiota hijacks this microenvironment-orchestrating machinery through metabolite-mediated inflammasome suppression, leading to distorted AMP balance favoring its preferential colonization. Restoration of the metabolite-inflammasome-AMP axis reinstates a normal microbiota and ameliorates colitis. Together, we identify microbial modulators of the NLRP6 inflammasome and highlight mechanisms by which microbiome-host interactions cooperatively drive microbial community stability through metabolite-mediated innate immune modulation. Therefore, targeted "postbiotic" metabolomic intervention may restore a normal microenvironment as treatment or prevention of dysbiosis-driven diseases.
                Bookmark

                Author and article information

                Contributors
                Journal
                Precis Clin Med
                Precis Clin Med
                pcm
                Precision Clinical Medicine
                Oxford University Press
                2096-5303
                2516-1571
                September 2022
                10 September 2022
                10 September 2022
                : 5
                : 3
                : pbac022
                Affiliations
                Institute of Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China , Hefei 230027, China
                Institute of Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China , Hefei 230027, China
                Institute of Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China , Hefei 230027, China
                Institute of Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China , Hefei 230027, China
                School of Data Science, University of Science and Technology of China , Hefei 230026, China
                Institute of Health and Medicine, Hefei Comprehensive National Science Center , Hefei 230051, China
                Author notes
                Correspondence: Shu Zhu, zhushu@ 123456ustc.edu.cn

                Runzhi Li and Yang Zan contributed equally to this work.

                Article
                pbac022
                10.1093/pcmedi/pbac022
                9536861
                36211635
                f26391f8-0634-4293-96b1-acab7cc9a259
                © The Author(s) 2022. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 15 June 2022
                : 05 September 2022
                : 06 October 2022
                Page count
                Pages: 5
                Funding
                Funded by: National Key Research and Development of China, DOI 10.13039/501100012166;
                Award ID: 2018YFA0508000
                Funded by: Chinese Academy of Sciences, DOI 10.13039/501100002367;
                Award ID: XDB29030101
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 82061148013
                Award ID: 81822021
                Award ID: 81821001
                Categories
                Minireview
                AcademicSubjects/MED00010

                nlrp6,inflammasome,phase separation,human disease
                nlrp6, inflammasome, phase separation, human disease

                Comments

                Comment on this article