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NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth
Open accessAbstract
Inflammatory bowel diseases involve the dynamic interaction of host genetics, the microbiome and inflammatory responses. Here we found lower expression of NLRP12 (which encodes a negative regulator of innate immunity) in human ulcerative colitis, by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12 deficiency in mice caused increased basal colonic inflammation, which led to a less-diverse microbiome and loss of protective gut commensal strains (of the family Lachnospiraceae) and a greater abundance of colitogenic strains (of the family Erysipelotrichaceae). Dysbiosis and susceptibility to colitis associated with Nlrp12 deficency were reversed equally by treatment with antibodies targeting inflammatory cytokines and by the administration of beneficial commensal Lachnospiraceae isolates. Fecal transplants from mice reared in specific-pathogen-free conditions into germ-free Nlrp12-deficient mice showed that NLRP12 and the microbiome each contributed to immunological signaling that culminated in colon inflammation. These findings reveal a feed-forward loop in which NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12 deficiency can reverse dysbiosis.
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“Interestingly, two previous studies have indicated that changes in the relative abundance of gut microbiota are more likely to be influenced by inflammation rather than age, with TNF playing a significant role.185,186”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [185]
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“Interestingly, two previous studies have indicated that changes in the relative abundance of gut microbiota are more likely to be influenced by inflammation rather than age, with TNF playing a significant role.(185,186) This suggests that the changes in gut microbiota are more closely related with inflammatory process…”
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“It has been shown to dampen and resolve inflammation, in particular in the intestine, in a microbiota dependent manner (228) and by promoting the growth of beneficial bacteria (228).”
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Self-citation
Metadata
- Authors
- Chen, L., Wilson, J. E., Koenigsknecht, M. J., Chou, W.-C., Montgomery, S. A., Truax, A. D., Brickey, W. J., Packey, C. D., Maharshak, N., Matsushima, G. K., Plevy, S. E., Young, V. B., Sartor, R. B., & Ting, J. P.-Y.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Michigan (US)
- Columbia University Irving Medical Center (US)
- Tel Aviv University (IL)
- Janssen (United States) (US)
- Corresponding author
- Ting, Jenny P-Y
- ORCID
- Venue
- Nature Immunology
- Published
- 2017-03-13
- Volume
- 18
- Issue
- 5
- Pages
- 541-551
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC5395345
- OpenAlex
- W2596103622
- Cited by
- 310
- References
- 51
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 35 · 2023: 34 · 2022: 32 · 2021: 30 · 2020: 39 · 2019: 42 · 2018: 31 · 2017: 16
- FWCI
- 14.30
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Crohn's and Colitis Foundation of America (P30 DK034987)
- North Carolina State University (P30 DK034987)
- Crohn's and Colitis Foundation
- Multiple Sclerosis Society
- National Institutes of Health (DK034987, DK094779, AI029564, AI067798, P40OD010995)
- National Cancer Institute (R01CA156330, P30CA016086)
- National Institute of Allergy and Infectious Diseases (U19AI090871, R37AI029564, AI-067798, U19AI067798)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK094779, F32DK098916, AI067798, P01DK094779, DK 034987, F32DK088417, P30DK034987)
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill (P30 DK 034987)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- NLRP12, inflammatory bowel disease, ulcerative colitis, colonic inflammation, gut microbiota, microbial diversity, commensal bacteria, Lachnospiraceae, Erysipelotrichaceae, dysbiosis, innate immunity, cytokine inhibition, fecal microbiota transplantation, germ-free mice, monozygotic twins
- MeSH terms
- Clostridiales, Eubacteriales, Firmicutes, Bacillota, Animals, Colitis, Ulcerative, Colon, Feces, Humans, Immunity, Innate, Mice, Inbred C57BL, RNA, Ribosomal, 16S, Symbiosis, Twins, Monozygotic, Dextran Sulfate, Mice, Knockout, Biodiversity, Intracellular Signaling Peptides and Proteins, Mice, Gene-Environment Interaction, Microbiota
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