ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Parasite and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1613297
This article is part of the Research TopicParasite-Induced Liver Diseases Volume IIView all 3 articles
IL-10/STAT5 Axis Suppresses miR-140 to Upregulate B7-H4 Expression in RAW264.7 cells
Provisionally accepted
- 1Nantong University, Nantong, China
- 2Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Schistosomiasis japonica, a zoonotic parasitic disease, induces complex immune regulation during infection. The inflammatory responses and immunosuppressive mechanisms co-exist to maintain immune homeostasis in schistosomiasis. B7-H4 is a critical immune checkpoint molecule that modulates T cell activation and exerts immunosuppressive effects. Our previous investigations revealed that B7-H4 mRNA expression was elevated in mice infected with Schistosoma japonicum, with interleukin-10 (IL-10) demonstrating regulatory capacity to enhance B7-H4 expression in RAW264.7 macrophages. In this study, we further explore the mechanism underlying IL-10-mediated B7-H4 upregulation.Notably, miR-140 was decreased in IL-10-treated microphages, accompanied by B7-H4 expression was upregulated. Through dualluciferase reporter assays, miR-140 can directly bind to the 3'UTR of B7-H4 and then inhibit the expression of B7-H4 in RAW264.7 cells.Meanwhile, miR-140 mimics can also attenuate IL-10-induced B7-H4 expression in RAW264.7 cells. Then we found that IL-10 may inhibit miR-140 promoter activity in RAW264.7 cells through transcription factors that binding to the -576/-94 bp region of the miR-140 promoter. Results by Western blot and ChIP further indicated that IL-10 could downregulate miR-140 promoter activity in a STAT5 dependence manner. After the sequence of STAT5 binding site within the -456/-446 bp region of the miR-140 promoter was mutated, IL-10 failed to suppress the activity produced by mutant miR-140 promoter. In conclusion, IL-10 can inhibit miR-140 through STAT5, thereby upregulating the expression of B7-H4 in RAW264.7 cells.
Keywords: ：miR-140, B7-H4, IL-10, Stat5, Schistosoma japonicum
Received: 17 Apr 2025; Accepted: 15 Jul 2025.
Copyright: © 2025 Zhu, Chen, Shen, Fan, Ji, Duan and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yinong Duan, Nantong University, Nantong, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.