Co-expression of master transcription factors determines CD4+ T cell plasticity and functions in auto-inflammatory diseases

Abstract

Master CD4⁺ T cell lineage determined transcription factors are found to be dysregulated in pathogenesis of autoimmune and inflammatory diseases. CD4⁺ T cells categorized into different lineages based on their functions, cell surface markers and master transcription factors those required for expression of lineage specific cytokines. T-bet, GATA3, RORγt and Foxp3 are major transcription regulators of Th1, Th2, Th17 and Treg cells respectively. Significant progress has been made in understanding expression of lineage specific master regulators that drives CD4⁺ T cell differentiation. It is known that each CD4⁺ T cell lineage express precise determined transcription factor and due to cross regulation between these factors the CD4⁺ T cells able to maintain thier specific phenotype. However, recent studies shows that the lineage specifying transcription factors frequently co-expressed. There is an emerging area of research revealing that the co-expression of lineage-specifying transcription factors alters the potential function and flexibility of subsets of CD4⁺ T cell, this in turn favors the autoimmune pathology. Here, we discuss similarities and differences between mutually co-expressed transcription factors in CD4⁺ T cell subsets and then recapitulates on cell type specific and dynamic balance between the lineage restricted transcription factors in determining plasticity of CD4⁺ T cell subsets. Furthermore, we discuss abnormal regulation of such transcription factors that establishes a pathogenic CD4⁺ T cell phenotype in autoimmune diseases and how this understanding will provide further insight into potential therapeutic development.

Keywords: Auto-inflammatory diseases; CD4(+) T cell; Cytokines; Pathogenic; Transcription factors.