Context- and cell-type specific function of miR155-Socs1 interaction in immune regulation

The microRNA (miRNA) dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3'' UTR of a major miR-155 target SOCS1 to specifically disrupt its regulation by miR-155. We found that under physiologic conditions and during autoimmune inflammation or viral infection some immunological functions of miR-155 were fully or largely attributable to the regulation of SOCS1, whereas others could be accounted only partially or not at all by this interaction. Our data suggest that the role of a single miRNA-mRNA interaction is cell type- and biological context-dependent. Overall design: Naïve WT, SOCS1KI and miR-155KO OVA-specific OT-1 TCR transgenic CD8+ T cells (1x10e4 per mouse) were adoptively transferred into CD45.1+ wt mice prior to infection with MCMV-OVA. WT, SOCS1KI and miR-155KO NK cells (2x10e5 per mouse) were adoptively transferred into CD45.1+ Klra8KO (Ly49H-deficient) mice prior to infection with MCMV. On d4 post infection, CD45.2+ CD44+ CD8+ OT-1 and CD45.2+ Ly49H+ NK1.1+ CD3- NK cells were FACS-sorted (BD FACS ARIA2). Each condition has 3 sequencing replicates.

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Lu LF, Gasteiger G, Yu IS, Chaudhry A, Hsin JP, Lu Y, Bos PD, Lin LL, Zawislak CL, Cho S, Sun JC, Leslie CS, Lin SW, Rudensky AY