Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival

Abstract

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but up-regulated in CD8+ T cells. CD4+ and CD8+ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4+ T cells. Transcriptome analysis of CD4+ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4+ T cells, but not in bystander CD4+ nor in CD8+ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150-/- antigen-specific CD4+ T. Thus, miR-150 impacts CD4+ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.

Circulating miRNAs Expression in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…The upregulation observed in our cohort of ME/CFS patients is in line with what was previously reported, showing that the overexpression of miR-150-5p in ME/CFS correlates with higher post-exertional malaise scores and symptom severity of patients [ 25 , 29 ]. This lymphopoietic-specific miRNA regulates many genes involved in the differentiation and proliferation of immune cells [ 35 , 50 ], and its pivotal role in autoimmune disease such as autoimmune pancreatitis, systemic SLE, primary Sjögren’s syndrome, and multiple sclerosis has been pointed out [ 51 , 52 , 53 ].…”

Highlight of 2023: big impacts of microRNAs in T cells

“…Notable were reports on miR‐150, miR‐15/16 and miR‐155, and how they regulate T‐cell biology in the context of disease, such as experimental autoimmune encephalomyelitis (EAE) and melanoma (Figure 1). 3–7 …”

“…miR‐150 and the miR‐15/16 microRNA clusters were identified as regulators of T‐cell survival and expansion. Ménoret et al 3 . reported that miR‐150 plays a role in promoting the apoptosis of antigen‐specific conventional CD4 + T cells after staphylococcal enterotoxin A immunization (Figure 1a).…”

“…reported that miR‐150 plays a role in promoting the apoptosis of antigen‐specific conventional CD4 + T cells after staphylococcal enterotoxin A immunization (Figure 1a). RNA‐sequencing analysis suggests that miR‐150 may exert its effects in these T cells via the mitochondria by downregulating the expression of genes associated with superoxide levels and apoptosis 3 . However, the precise targets of miR‐150 were not defined.…”