MicroRNA-155 Modulates Treg and Th17 Cells Differentiation and Th17 Cell Function by Targeting SOCS1

Abstract

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.

MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

“…Another important chemotactic factor for these cells, MCP-1 (CCL2), was also investigated in the nasopharynxes of WT and mir155KO mice; however, no differences were observed. As shown by our observations from Th17 polarization experiments, as well as previous studies (22), mir-155 is integral to the development of Th17 cells. The mechanism of this phenomenon is at least partly related to the repression of transcription factor Ets-1 (37), which is known to contribute to a myriad of cellular processes, including energy metabolism and innate in- flammatory response-related signaling (38).…”

“…For example, by repressing the transcripts encoding suppressor of cytokine signaling 1 and Src homology 2 domain-containing inositol 5-phosphatase 1, mir-155 promotes immunity to Staphylococcus aureus (19) and Francisella tularensis (20), respectively, but negatively impacts Mycobacterium tuberculosis infection (21). Mir-155 has also been reported to be integral in the development of IL-17A-producing CD4 ϩ T cells (Th17 cells) (22), mainly in the context of autoimmune inflammation (16,23), but also during gastrointestinal infection with Helicobacter pylori (24).…”

MicroRNA-155 Drives TH17 Immune Response and Tissue Injury in Experimental Crescentic GN

“…Mice deficient in T cell miRNAs have vital T helper cells with an impaired capacity to proliferate. 16 Moreover, individual miRNAs have been implicated in T cell function, especially in influencing T H 1 cells, 17 T H 17 cells, 18,19 and Treg cells. 20 Recently, miRNA-146 (miR-146) and miR-155 have been shown to be increased in both the urine and kidney of patients with IgA nephropathy.…”

MicroRNA-126, -145, and -155

“…42 Notably, miR-155 can promote the differentiation of regulatory T cells by targeting SOCS1. 49 Considering the upregulation of miR-155* in activated macrophages, a role of miR-155* in early atherosclerosis that opposes the effects of its sister strand, miR-155, as has been observed in dendritic cells, 50 may be hypothesized. In ECs, miR-155 is upregulated by high shear stress and targets the angiotensin II type 1 receptor and Ets-1, which reduces the proinflammatory activity of angiotensin II.…”