MicroRNA-150 controls differentiation of intraepithelial lymphocytes through TGF-β receptor II regulation

Sang Hwan Seo, Min Seong Jang, Doo Jin Kim, Seok Min Kim, Se Chan Oh, Cho Rok Jung, Yunji Park, Sang Jun Ha, Haiyoung Jung, Young Jun Park, Suk Ran Yoon, Inpyo Choi, Tae Don Kim

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2 Citations (Scopus)

Abstract

Background: Intraepithelial lymphocytes (IELs) in the intestines play pivotal roles in maintaining the integrity of the mucosa, regulating immune cells, and protecting against pathogenic invasion. Although several extrinsic factors, such as TGF-β, have been identified to contribute to IEL generation, intrinsic regulatory factors have not been determined fully. Objective: Here we investigated the regulation of IEL differentiation and the underlying mechanisms in mice. Methods: We analyzed IELs and the expression of molecules associated with IEL differentiation in wild-type control and microRNA (miRNA)-150 knockout mice. Methotrexate was administered to mice lacking miR-150 and control mice. Results: miR-150 deficiency reduced the IEL population in the small intestine and increased susceptibility to methotrexate-induced mucositis. Evaluation of expression of IEL differentiation–associated molecules showed that miR-150–deficient IELs exhibited decreased expression of TGF-β receptor (TGF-βR) II, CD103, CD8αα, and Runt-related transcription factor 3 in all the IEL subpopulations. The reduced expression of TGF-βRII in miR-150–deficient IELs was caused by increased expression of c-Myb/miR-20a. Restoration of miR-150 or inhibition of miR-20a recovered the TGF-βRII expression. Conclusion: miR-150 is an intrinsic regulator of IEL differentiation through TGF-βRII regulation. miR-150–mediated IEL generation is crucial for maintaining intestinal integrity against anticancer drug–induced mucositis.

Original languageEnglish
Pages (from-to)1382-1394.e14
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number4
DOIs
Publication statusPublished - 2018 Apr

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Seo, S. H., Jang, M. S., Kim, D. J., Kim, S. M., Oh, S. C., Jung, C. R., Park, Y., Ha, S. J., Jung, H., Park, Y. J., Yoon, S. R., Choi, I., & Kim, T. D. (2018). MicroRNA-150 controls differentiation of intraepithelial lymphocytes through TGF-β receptor II regulation. Journal of Allergy and Clinical Immunology, 141(4), 1382-1394.e14. https://doi.org/10.1016/j.jaci.2017.07.019