Long noncoding RNA LIRIL2R modulates FOXP3 levels and suppressive function of human CD4

Regulatory T cells (Tregs) are central in controlling immune responses, and dysregulation of their function can lead to autoimmune disorders or cancer. Despite extensive studies on Tregs, the basis of epigenetic regulation of human Treg development and function is incompletely understood. Long intergenic noncoding RNAs (lincRNA)s are important for shaping and maintaining the epigenetic landscape in different cell types. In this study, we identified a gene on the chromosome 6p25.3 locus, encoding a lincRNA, that was up-regulated during early differentiation of human Tregs. The lincRNA regulated the expression of interleukin-2 receptor alpha (IL2RA), and we named it the lincRNA regulator of IL2RA (LIRIL2R). Through transcriptomics, epigenomics, and proteomics analysis of LIRIL2R-deficient Tregs, coupled with global profiling of LIRIL2R binding sites using chromatin isolation by RNA purification, followed by sequencing, we identified IL2RA as a target of LIRIL2R. This nuclear lincRNA binds upstream of the

Déclaration de conflit d'intérêts

Competing interests statement:A.M. is a cofounder of Arsenal Biosciences, Function Bio, Spotlight Therapeutics, and Survey Genomics; serves on the boards of directors at Function Bio, Spotlight Therapeutics, and Survey Genomics; is a member of the scientific advisory boards of Arsenal Biosciences, Function Bio, Spotlight Therapeutics, Survey Genomics, NewLimit, Amgen, Tenaya, and Lightcast; owns stock in Arsenal Biosciences, Function Bio, Spotlight Therapeutics, NewLimit, Survey Genomics, Tenaya, and Lightcast; and has received fees from Arsenal Biosciences, Spotlight Therapeutics, NewLimit, Amgen, 23andMe, PACT Pharma, Juno Therapeutics, Tenaya, Survey Genomics, Lightcast, Gilead, Trizell, Vertex, Merck, Genentech, AlphaSights, Rupert Case Management, Bernstein, GLG, ClearView Healthcare Partners, and ALDA. A.M. is an investor in and informal advisor to Offline Ventures and a client of EPIQ. S.B.A.A., U.U.K., S.P., V.K., O.R., and R.L. are inventors in a European patent (Oligonucleotides for Modulating Regulatory T Cell Mediated Immunosuppression, patent number: WO2023242469A1) related to this manuscript. All other authors declare no competing interests.