CD4 T lymphocytes are highly efficient at protecting the host against a wide variety of endogenous and exogenous dangers, comprising tumors, viruses, bacteria and parasites. Their efficiency comes at least in part from their ability to adapt their phenotype and function to the nature of the threat. T lymphocytes indeed mobilize distinct gene expression programs which coordinate the acquisition of lineage-specific and danger-adapted phenotypes and functions. Naïve CD4 T cells are thus able to differentiate into distinct Thelper (“Th”) lymphocyte populations, including the so-called Th1, Th2, Th17 and Treg cells. Interplay of transcription factors and epigenetic mechanisms have a causal role in the regulation of Th lymphocytes gene expression programs. Interplay of transcription factors and epigenetic mechanisms, such as DNA methylation or post-translational histone modifications, have a causal role in the regulation of Th gene expression programs. Preliminary data from our group and emerging evidence from the literature suggest another layer of complexity in Th commitment and function as a result of epitranscriptomic modifications, i.e. dynamic chemical modifications of transcripts. It emerged as a new fundamental conserved mechanism involved in the control of cell differentiation and homeostasis. Half of known RNA modifications have already been linked to human diseases, including immune related diseases. Whereas several studies characterized an essential role of epitranscriptomic modifications in the regulation of different aspects of the immune system, the characterization of the majority of epitranscriptomic actors in Th subsets is still poorly understood, at least in part due to the lack of epitranscriptomic adapted study tools. Recently emerged a new method allowing accurate detection of all RNA modifications at single-base level in native full-length RNA transcripts using third-generation sequencing (Oxford Nanopore Technologies). The main objective of this project is to understand the respective role of RNA modifications related enzymes in Th subsets by combining in vitro and in vivo approaches as well as Nanopore sequencing. Extend our knowledge of the epitranscriptomic regulation of gene expression in Th cells could ultimately provide novel insights into the pathogenesis of autoimmune disorders and potential targets for epitranscriptomic therapy.