Recent evidence has shown that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4+ T cells remains largely unknown. Here we first found that the activation and proliferation, as well as the expression of
interferon (IFN)-γ, of CD4+ T cells from miR-126 knock-down (KD) mice using the
miRNA-sponge technique were enhanced significantly in vitro, compared with those in CD4+ T cells from wild-type (WT) mice. To monitor further the possible effect of miR-126 deficiency on the function of CD4+ T cells in vivo, we used
dextran sulphate
sodium (DSS)-induced murine model of acute autoimmune
colitis and found that miR-126 deficiency could elevate the pathology of
colitis. Importantly, the proportion of CD4+ T cells in splenocytes increased significantly in miR-126KD mice. Moreover, the expression levels of CD69 and CD44 on CD4+ T cells increased significantly and the expression level of CD62L decreased significantly. Of note, adoptive cell transfer assay showed that the pathology of
colitis was more serious in
carboxyfluorescein succinimidyl
ester (
CFSE)-labelled miR-126KD CD4+ T cell-transferred group, compared with that in the
CFSE-labelled WT CD4+ T cells transferred group. Consistently, the expression levels of CD69 and CD44 on CFSE+ cells increased significantly. Furthermore, both the proliferation and IFN-γ secretion of CFSE+ cells also increased significantly in the
CFSE-labelled miR-126KD CD4+ T cell-transferred group. Mechanistic evidence showed that the expression of
insulin receptor substrate 1 (IRS-1), as a functional target of miR-126, was elevated in CD4+ T cells from miR-126KD mice, accompanied by altered transduction of the extracellular regulated
kinase, protein B (AKT) and
nuclear factor kappa B (NF-κB) pathway. Our data revealed a novel role in which miR-126 was an intrinsic regulator in the function of CD4+ T cells, which provided preliminary basis for exploring further the role of miR-126 in the development, function of CD4+ T cells and related clinical diseases.