@article{3ae564fc26444923942bc1a7f392f042,
title = "NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth",
abstract = "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.",
author = "Liang Chen and Wilson, {Justin E.} and Koenigsknecht, {Mark J.} and Chou, {Wei Chun} and Montgomery, {Stephanie A.} and Truax, {Agnieszka D.} and Brickey, {W. June} and Packey, {Christopher D.} and Nitsan Maharshak and Matsushima, {Glenn K.} and Plevy, {Scott E.} and Young, {Vincent B.} and Sartor, {R. Balfour} and Ting, {Jenny P.Y.}",
note = "Funding Information: We thank the following for core and technical support: the University of North Carolina (UNC)–North Carolina State University Center for Gastrointestinal Biology and Disease; the UNC Microbiome Core Facility; S.L. Tonkonogy and the Gnotobiotic Core at North Carolina State University; M.A. Bower and J.W. Herzog at the National Gnotobiotic Rodent Resource Center and Crohn{\textquoteright}s and Colitis Foundation of America Gnotobiotic Animal Facility at UNC; the UNC Lineberger Comprehensive Cancer Center Animal Histopathology Core Facility and Animal Studies Core Facility; and the UNC Flow Cytometry Core Facility. Supported by the US National Institute of Health (RO1-CA156330 to J.P.-Y.T. (National Cancer Institute); P01 DK094779 to J.P.-Y.T., P30 DK034987 to R.B.S., F32-DK088417-01 to J.E.W. and F32-DK098916 to A.D.T. (National Institute of Diabetes and Digestive and Kidney Diseases); U19-AI067798 and R37 AI029564 to J.P.-Y.T. and U19 AI090871 to V.B.Y. (National Institute of Allergy and Infectious Disease); and P40 OD010995 to R.B.S. (Office of the Director)), the American Cancer Society (PF-13-401-01-TBE to J.E.W.), the Crohn{\textquoteright}s and Colitis Foundation of America (R.B.S.) and the National Multiple Sclerosis Society (FG 1968-A-1 to W-C.C.). Funding Information: Supported by the US National Institute of Health (RO1-CA156330 to J.P.-Y.T. (National Cancer Institute); P01 DK094779 to J.P.-Y.T., P30 DK034987 to R.B.S., F32-DK088417-01 to J.E.W. and F32-DK098916 to A.D.T. (National Institute of Diabetes and Digestive and Kidney Diseases); U19-AI067798 and R37 AI029564 to J.P.-Y.T. and U19 AI090871 to V.B.Y. (National Institute of Allergy and Infectious Disease); and P40 OD010995 to R.B.S. (Office of the Director)), the American Cancer Society (PF-13-401-01-TBE to J.E.W.), the Crohn's and Colitis Foundation of America (R.B.S.) and the National Multiple Sclerosis Society (FG 1968-A-1 to W-C.C.). Publisher Copyright: {\textcopyright} 2017 Nature America, Inc.",
year = "2017",
month = apr,
day = "18",
doi = "10.1038/ni.3690",
language = "English (US)",
volume = "18",
pages = "541--551",
journal = "Nature immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "5",
}