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A T-cell specific lncRNA LINC01871 is induced upon T cell activation and during beta-cell autoimmunity

ABSTRACT: Long intergenic noncoding RNAs (lincRNAs) regulate biological processes in health and disease. However, little is known about the contribution of lincRNAs in T-cell activation. Here we found a lincRNA, LINC01871, that is highly induced upon T-cell activation and is primarily located in the cytoplasm. The anti-inflammatory cytokine TGF-β negatively regulates its expression. Its expression is quite specific to different T cell populations among all tissues and cell types. Silencing LINC01871 led to a modest reduction in IL-2 secretion. RNA-seq and proteomic analysis of LINC01871-deficient CD4+ T cells identified its targets, including ATG2B; TRIM5; SNX30; TIMM8B; and ATP10A. Importantly, LINC01871 expression was very specific to T cells in several cross tissue single cell RNA-seq datasets. Further, expression of LINC01871 was higher in ex-vivo CD4+ T cells from children progressing to beta-cell autoimmunity compared to their respective age, sex and HLA-risk matched controls, suggesting that the lincRNA has an in-vivo function in T-cell-mediated immunity. Further, LINC01871 expression was associated with the age, and it was higher in males than females.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Blood

SUBMITTER: Kedar Batkulwar

LAB HEAD: Riitta Lahesmaa

PROVIDER: PXD052298 | Pride | 2025-08-27

REPOSITORIES: Pride

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			Action	DRS
	20240515_132236_220803_LincAH2_Proteomics.sne	Other
	220803_AH2_LNA2_R1.htrms	Other
	220803_AH2_LNA2_R1.raw	Raw
	220803_AH2_LNA2_R2.htrms	Other
	220803_AH2_LNA2_R2.raw	Raw

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Project description:Naive CD4+ T cells are the common precursors of multiple effector and memory T cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4+ T cells and their changes during the early phase of T cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy.<br>Periodate oxidation and aniline-catalyzed oxime ligation (PAL) technology was applied with subsequent quantitative LC-MS/MS (PAL-qLC-MS/MS) to generate a dataset describing the surface proteome of human naive CD4+ T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins, of which 24 were previously not known to be expressed on human naive CD4+ T cells or have no defined role within T cell activation. To independently confirm the proteomic dataset and to analyse the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous dataset, resulting in 229 surface proteins which are expressed on naive unstimulated and activated CD4+ T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation and predicted subcellular localization, and correlated the proteomics result with this transcriptional dataset.<br>This extensive surface atlas provides an overall naive CD4+ T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments.

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A T-cell specific lncRNA LINC01871 is induced upon T cell activation and during beta-cell autoimmunity

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