MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus

Richa Mishra; Sanjana Bhattacharya; Bhupendra Singh Rawat; Ashish Kumar; Akhilesh Kumar; Kavita Niraj; Ajit Chande; Puneet Gandhi; Dheeraj Khetan; Amita Aggarwal; Seiichi Sato; Prafullakumar Tailor; Akinori Takaoka; Himanshu Kumar

doi:10.1016/j.isci.2020.101322

MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus

iScience. 2020 Jul 24;23(7):101322. doi: 10.1016/j.isci.2020.101322. Epub 2020 Jul 1.

Authors

Affiliations

¹ Laboratory of Immunology and Infectious Disease Biology, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, AB-3, Room No. 215, Bhopal By-pass Road, Bhauri, Bhopal, MP 462066, India.
² Laboratory of Innate Immunity, National Institute of Immunology (NII), New Delhi 110067, India.
³ Department of Research (Medical Biotechnology), Bhopal Memorial Hospital & Research Centre (BMHRC), Bhopal, MP 462038, India.
⁴ Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, MP 462066, India.
⁵ Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP 226014, India.
⁶ Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP 226014, India.
⁷ Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
⁸ Laboratory of Immunology and Infectious Disease Biology, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, AB-3, Room No. 215, Bhopal By-pass Road, Bhauri, Bhopal, MP 462066, India; WPI Immunology, Frontier Research Centre, Osaka University, Osaka 5650871, Japan. Electronic address: hkumar@iiserb.ac.in.

Abstract

Precise regulation of innate immunity is crucial for development of appropriate host immunity against microbial infections and maintenance of immune homeostasis. MicroRNAs are small non-coding RNAs, post-transcriptional regulator of multiple genes, and act as a rheostat for protein expression. Here, we identified microRNA-30e-5p induced by hepatitis B virus and other viruses that act as a master regulator for innate immunity. Moreover, pegylated interferons treatment of patients with HBV for viral reduction also reduces miRNA. Additionally, we have also shown the immuno-pathological effects of miR-30e in patients with systemic lupus erythematosus (SLE) and mouse model. Mechanistically, miR-30e targets multiple negative regulators of innate immune signaling and enhances immune responses. Furthermore, sequestering of miR-30e in patients with SLE and mouse model significantly reduces type-I interferon and pro-inflammatory cytokines. Collectively, our study demonstrates the novel role of miR-30e in innate immunity and its prognostic and therapeutic potential in infectious and autoimmune diseases.

Keywords: Immunology; Virology.