Role of microRNAs and long‐non‐coding RNAs in CD4⁺ T‐cell differentiation

Abstract

CD4(+) T lymphocytes orchestrate adaptive immune responses by differentiating into various subsets of effector T cells such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells. These subsets have been generally described by master transcription factors that dictate the expression of cytokines and receptors, which ultimately define lymphocyte effector functions. However, the view of T-lymphocyte subsets as stable and terminally differentiated lineages has been challenged by increasing evidence of functional plasticity within CD4(+) T-cell subsets, which implies flexible programming of effector functions depending on time and space of T-cell activation. An outstanding question with broad basic and traslational implications relates to the mechanisms, besides transcriptional regulation, which define the plasticity of effector functions. In this study, we discuss the emerging role of regulatory non-coding RNAs in T-cell differentiation and plasticity. Not only microRNAs have been proven to be important for CD4(+) T-cell differentiation, but it is also likely that the overall T-cell functioning is the result of a multilayered network composed by coding RNAs as well as by short and long non-coding RNAs. The integrated study of all the nodes of this network will provide a comprehensive view of the molecular mechanisms underlying T-cell functions in health and disease.

Th1/Th2 Cell Differentiation and Molecular Signals

“…2.2). [123]. Tmevpg1 in blue is a long intergenic noncoding RNA has the influence on the Th1 cell [30].…”

Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

“…Specifically, LncR-Ccr2-5' AS, together with GATA-3, is essential in the regulatory circuit in gene expression specific to the migration of Th2 cells [20]. Such roles of lncRNAs were also found in CD8 + T cell [21] and CD4 + T cell polarization [22,23]. More importantly, lncRNAs also play essential roles on macrophage polarization.…”

Mutual interaction between BCL6 and microRNAs in T cell differentiation

“…In conclusion, BCL6 interacts with various miRNAs and plays a key role in the differentiation of T cell subtypes, [73][74][75][76] mainly by regulating gene expression in T subtypes via a mutual interaction between BCL6 and the miRNAs. To broadly support the idea that BCL6 regulate miRNAs, chromatin immunoprecipitation-sequencing (ChIP-Seq) should be performed for BCL6 in T cells and mechanistic studies should be carried out.…”