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

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, ROR gamma t 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.