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Intestinal Epithelial Cell-Derived LKB1 Suppresses Colitogenic Microbiota.


ABSTRACT: Dysregulation of the immune barrier function of the intestinal epithelium can often result in dysbiosis. In this study we report a novel role of intestinal epithelial cell (IEC)-derived liver kinase B1 (LKB1) in suppressing colitogenic microbiota. IEC-specific deletion of LKB1 (LKB1?IEC) resulted in an increased susceptibility to dextran sodium sulfate (DSS)-induced colitis and a definitive shift in the composition of the microbial population in the mouse intestine. Importantly, transfer of the microbiota from LKB1?IEC mice was sufficient to confer increased susceptibility to DSS-induced colitis in wild-type recipient mice. Collectively, the data indicate that LKB1 deficiency in intestinal epithelial cells nurtures the outgrowth of colitogenic bacteria in the commensal community. In addition, LKB1 deficiency in the intestinal epithelium reduced the production of IL-18 and antimicrobial peptides in the colon. Administration of exogenous IL-18 restored the expression of antimicrobial peptides, corrected the outgrowth of several bacterial genera, and rescued the LKB1?IEC mice from increased sensitivity to DSS challenge. Taken together, our study reveals an important function of LKB1 in IECs for suppressing colitogenic microbiota by IL-18 expression.

SUBMITTER: Liu X 

PROVIDER: S-EPMC6814173 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Intestinal Epithelial Cell-Derived LKB1 Suppresses Colitogenic Microbiota.

Liu Xia'nan X   Lu Jinfeng J   Liu Zhenshan Z   Zhao Junjie J   Sun Hongxiang H   Wu Ningbo N   Liu Hongzhi H   Liu Weiwei W   Hu Zhuqin Z   Meng Guangxun G   Shen Lei L   Miller Aaron W AW   Su Bing B   Li Xiaoxia X   Kang Zizhen Z  

Journal of immunology (Baltimore, Md. : 1950) 20180119 5


Dysregulation of the immune barrier function of the intestinal epithelium can often result in dysbiosis. In this study we report a novel role of intestinal epithelial cell (IEC)-derived liver kinase B1 (LKB1) in suppressing colitogenic microbiota. IEC-specific deletion of LKB1 (LKB1<sup>ΔIEC</sup>) resulted in an increased susceptibility to dextran sodium sulfate (DSS)-induced colitis and a definitive shift in the composition of the microbial population in the mouse intestine. Importantly, trans  ...[more]

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