The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated...The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated molecular patterns(PAMPs).展开更多
Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer.However,key host factors that may control the generation of the inner mucus layer are rarely reported.Here,we identify ...Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer.However,key host factors that may control the generation of the inner mucus layer are rarely reported.Here,we identify a novel function of TRIM34 in goblet cells(GCs)in controlling inner mucus layer generation.Upon DSS treatment,TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer.This outcome rendered TRIM34-deficient mice more susceptible to DSS-induced colitis and colitis-associated colorectal cancer.Mechanistic experiments demonstrated that TRIM34 controlled TLR signaling-induced Nox/Duox-dependent ROS synthesis,thereby promoting the compound exocytosis of Muc2 by colonic GCs that were exposed to bacterial TLR ligands.Clinical analysis revealed that TRIM34 levels in patient samples were correlated with the outcome of ulcerative colitis(UC)and the prognosis of rectal adenocarcinoma.This study indicates that TRIM34 expression in GCs plays an essential role in generating the inner mucus layer and preventing excessive colon inflammation and tumorigenesis.展开更多
文摘The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated molecular patterns(PAMPs).
基金We thank Dangsheng Li for critical suggestions.We are grateful to Guomei Lin for breeding the animals and Li Li for animal management.We also acknowledge the individuals involved in technical support at the Core Facility for Cell Biology and the Animal Core Facility.This work was supported by grants from the National Key Research and Development Program of China(2018YFA0507402)the National Natural Science Foundation of China(31230024)+1 种基金the Chinese Academy of Sciences(XDB19000000)the National Natural Science Foundation of China(81761128009 and 81630016).
文摘Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer.However,key host factors that may control the generation of the inner mucus layer are rarely reported.Here,we identify a novel function of TRIM34 in goblet cells(GCs)in controlling inner mucus layer generation.Upon DSS treatment,TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer.This outcome rendered TRIM34-deficient mice more susceptible to DSS-induced colitis and colitis-associated colorectal cancer.Mechanistic experiments demonstrated that TRIM34 controlled TLR signaling-induced Nox/Duox-dependent ROS synthesis,thereby promoting the compound exocytosis of Muc2 by colonic GCs that were exposed to bacterial TLR ligands.Clinical analysis revealed that TRIM34 levels in patient samples were correlated with the outcome of ulcerative colitis(UC)and the prognosis of rectal adenocarcinoma.This study indicates that TRIM34 expression in GCs plays an essential role in generating the inner mucus layer and preventing excessive colon inflammation and tumorigenesis.
