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.

26Precise regulation of innate immunity is crucial for the development of appropriate host 27 immunity against microbial infections and the maintenance of immune homeostasis. The 28 microRNAs are small non-coding RNA, post-transcriptional regulator of multiple genes and 29 act as a rheostat for protein expression. Here, we identified microRNA(miR)-30e-5p (miR-30 30e) induced by the hepatitis B virus (HBV) and other viruses that act as a master regulator 31 for innate immune responses. Moreover, pegylated type I interferons treatment to HBV 32 patients for viral reduction also reduces the miRNA. Additionally, we have also shown the 33 immuno-pathological effects of miR-30e in systemic lupus erythematous (SLE) patients and 34 SLE mouse model. Mechanistically, the miR-30e targets multiple negative regulators namely 35

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