MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1

• Published in: PloS one 2012-10, Vol.7 (10), p.e46082-e46082
• Main Authors: Yao, Rui, Ma, Yu-Lan, Liang, Wei, Li, Huan-Huan, Ma, Zhi-Jun, Yu, Xian, Liao, Yu-Hua
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Analysis; Animals; Atherosclerosis; Base Sequence; Biology; Cardiology; CD25 antigen; CD4 antigen; Cell differentiation; Cell Differentiation - genetics; Cell lineage; Cytokines; Differentiation (biology); Forkhead Transcription Factors - genetics; Function analysis; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Gene expression; Gene Expression Regulation; Genetic aspects; Growth factors; Helper cells; Homology; Immune response; Immune system; Immunology; Inflammatory diseases; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin 10; Interleukin-10 - metabolism; Interleukin-17 - metabolism; Interleukin-4 - genetics; Interleukin-4 - metabolism; Janus kinase; Janus Kinases - metabolism; Laboratories; Lupus; Lymphocytes; Lymphocytes T; Medicine; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Physiological aspects; Ribonucleic acid; RNA; Science; Signal Transduction; Signaling; Smad protein; Smad Proteins - metabolism; Smad2 protein; Smad5 protein; STAT Transcription Factors - metabolism; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Suppressors; T cell receptors; T cells; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - metabolism; Th17 Cells - cytology; Th17 Cells - metabolism; Transcription; Transcription factors; Transfection; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046082

MicroRNA (miR)-155 is a critical player in both innate and adaptive immune responses. It can influence CD4(+) T cell lineage choice. To clarify the role of miR-155 in CD4(+) CD25(+) regulatory T (Treg)/T helper (Th)17 cell differentiation and function, as well as the mechanism involved, we performed gain-and loss-of-function analysis by transfection pre-miR-155 and anti-miR-155 into purified CD4(+) T cells. The results showed that miR-155 positively regulated both Treg and Th17 cell differentiation. It also induced the release of interleukin (IL)-17A by Th17 cells, but not the release of IL-10 and transforming growth factor (TGF)-β1 by Treg cells. Furthermore, we found that miR-155 reacted through regulating Janus kinase/signal transducer and activator of transcription (JAK/STAT) rather than TGF-β/mothers against decapentaplegic homolog (SMAD) signaling pathway in the process of Treg and Th17 cells differentiation. This may because suppressors of cytokine signaling (SOCS)1, the important negative regulator of JAK/STAT signaling pathway, was the direct target of miR-155 in this process, but SMAD2 and SMAD5 were not. Therefore, we demonstrated that miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by targeting SOCS1.