Drosophila Relish‐mediated miR‐317 expression facilitates immune homeostasis restoration via inhibiting PGRP‐LC. Issue 12 (17th October 2022)

• Record Type: Journal Article
• Authors: Zhou, Hongjian; Wu, Shanshan; Liu, Li; Liu, Xiaoqi; Lan, Siyu; Jiang, Jiajun; Yang, Wan; Jin, Ping; Xia, Xinyi; Ma, Fei
• Is Part Of: European journal of immunology. Volume 52:Issue 12(2022)
• Page Start: 1934
• Page End: 1945
• Publication Date: 2022-10-17
• Subjects: Drosophila melanogaster -- Imd signaling pathway -- immune homeostasis restoration -- miR‐317 -- Relish; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202250034
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Innate immunity is the first and essential line for resisting pathogens, and the immune intensity and duration need to be strictly regulated to balance excessive or insufficient immune response. MicroRNAs (miRNAs) are crucial regulators of immune response in Drosophila, yet how immune‐related miRNAs are regulated remains poorly understood. Herein, we elucidated that the involvement of miR‐317 in NF‐κB transcription factor Relish mediated Drosophila Imd pathway in response to Gram‐negative (G‐) bacteria stimulation. Remarkably, the dynamic expression profiling for immune response indicated that Relish simultaneously enhances the expression of the effector antimicrobial peptide Dpt as well as miR‐317 post‐infection. Upregulation of miR‐317 could further down‐regulate the expression of PGRP‐LC, thereby forming a feedback in Drosophila Imd pathway to prevent over‐activation and restore immune homeostasis. Taken together, our study not only uncovers a novel Relish/miR‐317/PGRP‐LC regulatory axis to attenuate Drosophila Imd immune response and facilitate immune homeostasis restoration, but also provides vital insights into the complex mechanisms of animal innate immune regulation. Abstract : When attacked by Gram‐negative bacteria, the Drosophila Imd pathway is activated and the NF‐κB transcription factor Rel68 enters the nucleus to simultaneously enhance the expression of the effector Dpt and miR‐317. Upregulation of the latter inhibits the expression of PGRP‐LC, thereby attenuating the Imd immune response and promoting Drosophila immune homeostasis restoration.