Quantifying long non-coding RNA expression in T helper 2 cell differentiation

Abstract

Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that lack protein-coding potential. LncRNAs have key roles in gene regulatory networks, and they have emerged as important regulators of cellular processes like differentiation. Despite this, their role in T cell differentiation and immune-related diseases remains poorly understood. The aim of this study was to investigate the expression of known and novel lncRNAs during differentiation of T helper type 2 (Th2) cells, and to explore their potential biological functions using computational approaches. LncRNA expression was quantified in a longitudinal dataset of in vitro differentiated Th2 cells, and lncRNAs with distinct expression patters during differentiation were identified. A subset of these lncRNAs was found within a Th2-associated co-expression module enriched for genes involved in immune function and cellular differentiation. The expression of candidate lncRNAs was validated in an independent bulk RNA-sequencing dataset comprising ex vivo isolated T cell subtypes, as well as at single-cell resolution in allergen reactive CD4+ T cells. This study provides a curated set of lncRNAs associated with Th2 cell differentiation and offers a foundation for future functional investigation, potentially contributing to the development of targeted therapeutic strategies and improved molecular stratification of immune-mediated diseases such as allergic asthma.