Journal
CYTOKINE
Volume 153, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2022.155841
Keywords
Interleukin-6; Intestine; Gut microbiota; Intraepithelial lymphocytes; Paneth cells; alpha-defensins
Funding
- Medical Science and Technique Foundation for Fostering Young Scientist [18QNP026]
- Basic research program of Natural Science in Shaanxi Province [2021JM-081]
- Funding Program for Medical Science Development of FMMU [2018HKPY02, 2020rcfczr]
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This study reveals the important role of IL-6 in mucosal immune cells and its interaction with gut microbiota. IL-6 loss can alter the composition of gut microbiota and affect the maintenance of immune cells, triggering mucosal immune response.
Interleukin-6 (IL-6) in mucosal immune cells is involved in post-injury intestinal regeneration, inflammation responses, and gastric homeostasis. However, the interaction between IL-6 and the dynamic balance of gut microbiota (GM) remains unexplored. Intestinal pathology was assessed by hematoxylin and eosin and periodic acid-Schiff staining in wild-type (WT) and IL-6 gene knockout (KO) C57BL/6J mice. GM profiles were established via high-throughput sequencing of the fecal bacterial 16S rRNA gene. Intestinal alpha-and beta-defensins were measured by quantitative real-time PCR; further, flow cytometry was performed to analyze isolated intraepithelial lymphocytes (IELs). Compared with the WT, IL-6 KO did not obviously change gut structures, but significantly reduced GM diversity, resulting in reduced metabolic pathways with decreased gram-positive but elevated gram-negative bacteria. More taxa alterations included differences at the phyla (e.g., increased Verrucomicrobia and decreased Firmicutes) and genera (e.g., increased Akkermansia and decreased Lactobacillus) levels. Absence of IL-6 also significantly increased intestinal expression of defensins alpha 3 and alpha 4 (Defa3 and Defa4) and the percentage of natural TCR gamma delta(+) IELs, providing a molecular basis for triggering mucosal immune response. Therefore, IL-6 loss remodels GM composition and alters IEL maintenance, identifying IL-6 as a crucial cytokine for GM dysbiosis and mucosal immunity.
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