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
Affiliations
Richa Mishra
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
Sanjana Bhattacharya
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
Bhupendra Singh Rawat
Laboratory of Innate Immunity, National Institute of Immunology (NII), New Delhi 110067, India
Ashish Kumar
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
Akhilesh Kumar
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
Kavita Niraj
Department of Research (Medical Biotechnology), Bhopal Memorial Hospital & Research Centre (BMHRC), Bhopal, MP 462038, India
Ajit Chande
Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, MP 462066, India
Puneet Gandhi
Department of Research (Medical Biotechnology), Bhopal Memorial Hospital & Research Centre (BMHRC), Bhopal, MP 462038, India
Dheeraj Khetan
Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP 226014, India
Amita Aggarwal
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP 226014, India
Seiichi Sato
Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
Prafullakumar Tailor
Laboratory of Innate Immunity, National Institute of Immunology (NII), New Delhi 110067, India
Akinori Takaoka
Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
Himanshu Kumar
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; Corresponding author
Summary: 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.
