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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Immunol
2017 ; 18
(5
): 541-551
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NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity
and promoting protective commensal bacterial growth
#MMPMID28288099
Chen L
; Wilson JE
; Koenigsknecht MJ
; Chou WC
; Montgomery SA
; Truax AD
; Brickey WJ
; Packey CD
; Maharshak N
; Matsushima GK
; Plevy SE
; Young VB
; Sartor RB
; Ting JP
Nat Immunol
2017[May]; 18
(5
): 541-551
PMID28288099
show ga
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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