Hepatology
Hepatology
3 years ago

MiR-15a/16-1 Suppresses AHR-dependent IL-22 Secretion in CD4(+) T cells and Contributes to Immune-mediated Organ Injury.

Lu, Huang, Chu, Liu, Qian, Zhang, Yang
Interleukin-22 (IL-22), as a link between leukocytic and non-leukocytic cells, has gained increasing attention for its pronounced tissue-protective properties. MicroRNAs (miRNAs), emerging as crucial immune modulators, have been reported to be involved in the production and action of various cytokines. However, the precise control of IL-22 by miRNAs and its subsequent actions remained to be elucidated. In this study, we found a negative correlation between the expression of miR-15a/16-1 and IL-22 in the model of concanavalinA (ConA)-induced immune-mediated liver injury. Knockout of miR-15a/16-1 (miR-15a/16-1-KO) ameliorated liver injury in an IL-22-dependent manner. Further results revealed that CD4(+) T cells were the major source of IL-22 during liver injury, and aryl hydrocarbon receptor (AHR) was the direct target of miR-15a/16-1 in CD4(+) T cells. In vivo and in vitro data showed that miR-15a/16-1-KO CD4(+) T cells produced more IL-22, while overexpression of miR-15a/16-1 downregulated the IL-22 production by inhibiting AHR. Moreover, transfer of miR-15a/16-1-KO CD4(+) T cells promoted tissue repair compared to wild type CD4(+) T cells by upregulating IL-22. In addition, as a synergistic effect, IL-22 could downregulate miR-15a/16-1 expression via activating pSTAT3/c-myc signaling, and the decrease of miR-15a/16-1 in damaged hepatocytes contributed to IL-22-mediated tissue repair by reducing cell apoptosis and promoting cell proliferation. As further proof, we demonstrated the role of miR-15a/16-1 in controlling IL-22 production and IL-22-mediated reconstruction of intestinal epithelial barrier in a dextran sodium sulphate-induced colitis model.

Publisher URL: http://doi.org/10.1002/hep.29573

DOI: 10.1002/hep.29573

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.