Effect of LINC01871 silencing on CD4+ T cell activation.

Long intergenic noncoding RNAs (lincRNAs) play crucial roles in regulating biological processes in health and disease. However, little is known about the contribution of lincRNAs in T-cell activation. Here, we identified a lincRNA, LINC01871, which is highly induced upon T-cell activation and is predominantly located in the cytoplasm. The anti-inflammatory cytokine TGF-ß was found to suppress its expression. Silencing LINC01871 led to a modest decrease in IL-2 secretion. RNA-seq and proteomic analyses of LINC01871-deficient CD4+ T cells revealed several targets, including genes associated with autophagy and membrane organization such as ATG2B; TRIM5; SNX30; TIMM8B; and ATP10A. Notably, LINC01871 expression was highly specific to T cells in several cross tissue single cell RNA-seq atlases. Furthermore, ex-vivo CD4+ T cells from children progressing to beta-cell autoimmunity showed higher LINC01871 expression as compared to their age, sex and HLA-risk matched controls. These data suggest that LINC01871 has an in-vivo function in T-cell-mediated immunity. Overall design: CD4 T cells were isolated using magnetic bead-based positive selection kit from Dynal. Cells were nucleofected with the three antisense locked nuelceic acid (LNAs) targeting the lincRNA LINC01871 or non targeting control LNAs (NT). After 24 hours of rest, cells were activated with CD3/CD28 for 48 hours. The cells were then reactivated for 30 minutes and RNA samples were extracted. There were three biological replicates* three LNAs =9 samples.