Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

The innate immune receptor NLRP12 maintains intestinal homeostasis by regulating microbiome diversity

Cellular & Molecular Immunology volume 15, pages 193–195 (2018)Cite this article

Inflammatory bowel disease (IBD) is on the rise in the western world.1 The dynamic interplay between genetic susceptibility, the gut microbiome and host inflammatory reactions underlying IBD are still unclear. Shedding light onto these complex interactions in IBD, Chen et al.2 identified a key role for the negative immune regulator NLRP12 in shaping the composition of the gut microbiome and maintaining intestinal homeostasis. This finding, published in the most recent issue of Nature Immunology,2 can advance the development of much needed microbiome-based therapies for IBD patients.

It has been estimated that IBD affects over 3 million patients worldwide, particularly in western countries.1, 3 IBD includes ulcerative colitis (UC) and Crohn's disease, and is associated with increased risk of gastrointestinal cancers such as colorectal cancer.4 IBD is an immunologically driven, multifactorial disease with the complex involvement of genetics, environmental factors and gut microbiota.1, 5 While the exact cause is not well understood, it is accepted that dysbiosis—the imbalance of the gut microbiota toward colitogenic strains—is associated with IBD. This is of particular importance as recent advances point to an ever-increasing role of the microbiota in host immune regulation,5 and as shown by Chen et al.,2 vice versa. Microbiome-based therapies thus hold promise to advance treatment options not only for IBD patients but also perhaps other immune disorders.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Kaplan GG . The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015; 12: 720–727.

    Article  Google Scholar 

  2. Chen L, Wilson JE, Koenigsknecht MJ, Chou WC, Montgomery SA, Truax AD et al. NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat Immunol 2017; 18: 541–551.

    Article  Google Scholar 

  3. Ananthakrishnan AN . Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015; 12: 205–217.

    Article  Google Scholar 

  4. Waldner MJ, Neurath MF . Mechanisms of immune signaling in colitis-associated cancer. Cell Mol Gastroenterol Hepatol 2015; 1: 6–16.

    Article  Google Scholar 

  5. Shi Y, Mu L . An expanding stage for commensal microbes in host immune regulation. Cell Mol Immunol 2017; 14: 339–348.

    Article  CAS  Google Scholar 

  6. Zambetti LP, Mortellaro A . NLRPs, microbiota, and gut homeostasis: unravelling the connection. J Pathol 2014; 233: 321–330.

    Article  CAS  Google Scholar 

  7. Williams TM, Leeth RA, Rothschild DE, Coutermarsh-Ott SL, McDaniel DK, Simmons AE et al. The NLRP1 inflammasome attenuates colitis and colitis-associated tumorigenesis. J Immunol 2015; 194: 3369–3380.

    Article  CAS  Google Scholar 

  8. Corridoni D, Arseneau KO, Cifone MG, Cominelli F . The dual role of nod-like receptors in mucosal innate immunity and chronic intestinal inflammation. Front Immunol 2014; 5: 317.

    Article  Google Scholar 

  9. Tuncer S, Fiorillo MT, Sorrentino R . The multifaceted nature of NLRP12. J Leukoc Biol 2014; 96: 991–1000.

    Article  Google Scholar 

  10. Zaki MH, Man SM, Vogel P, Lamkanfi M, Kanneganti TD . Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. Proc Natl Acad Sci USA 2014; 111: 385–390.

    Article  CAS  Google Scholar 

  11. Allen IC, Wilson JE, Schneider M, Lich JD, Roberts RA, Arthur JC et al. NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-kappaB signaling. Immunity 2012; 36: 742–754.

    Article  CAS  Google Scholar 

  12. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 2011; 145: 745–757.

    Article  CAS  Google Scholar 

  13. Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M . Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014; 104: Unit 15.25.

    PubMed  PubMed Central  Google Scholar 

  14. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR . Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 2007; 104: 13780–13785.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Experimental Medicine, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast, BT9 7BL, UK

    Jenny Moi-Fong Lau & Yvonne Dombrowski

Authors
  1. Jenny Moi-Fong Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvonne Dombrowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yvonne Dombrowski.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lau, JF., Dombrowski, Y. The innate immune receptor NLRP12 maintains intestinal homeostasis by regulating microbiome diversity. Cell Mol Immunol 15, 193–195 (2018). https://doi.org/10.1038/cmi.2017.61

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2017.61

This article is cited by

Search

Advanced search

Quick links