title: The crosstalk between IL-22 signaling and miR-197 in human keratinocytes.
abstract: The interaction between the immune system and epithelial cells is tightly regulated. Aberrations of this balance may result in inflammatory diseases such as psoriasis, inflammatory bowel disease and rheumatoid arthritis. IL-22 is produced by Th17, Th22 and Th1 cells. Putative targets for IL-22 are cells in the skin, kidney, digestive and respiratory systems. The highest expression of IL-22 receptor is found in the skin. IL-22 plays an important role in the pathogenesis of T cell-mediated inflammatory diseases such as psoriasis, inflammatory bowel disease and rheumatoid arthritis. Recently, we found that miR-197 is down regulated in psoriatic lesions. In the present work we show that miR-197 over expression inhibits keratinocytes proliferation induced by IL-22 and keratinocytes migration. In addition, we found that IL-22 activates miR-197 expression through the binding of phosphorylated STAT3 to sequences in the putative promoter of miR-197. Finally we found that IL-22 receptor subunit IL22RA1 is a direct target of miR-197. Hence, we identified a novel feedback loop controlling IL-22 signaling, in which IL-22 induces miR-197, which in turn, negatively regulates IL-22 receptor and attenuates the biological outcome of such signaling. Regulation of this pathway may be important in inflammatory skin disorders such a psoriasis and in wound healing.
authors.affiliation: Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Galya
authors.initials: G
authors.lastname: Lerman
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Sharon
authors.affiliation: Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel; Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Raya
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.affiliation: Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Sidi
authors.affiliation: Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Avni
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C546085:MIRN197 microRNA, human; C494086:STAT3 protein, human