FIGURE 2. Transcriptional regulation of CD4⁺ T helper (T_H) cells that mediate tissue inflammation.

CD4⁺ T_H cells are a heterogeneous population of effector cells with a significant degree of genetic plasticity that enables them to acquire effector functions and the cytokine profiles of the opposing T_H lineages. Generally, CD4⁺ T_H plasticity is associated with more aggressive CD4⁺ T_H responses and destructive inflammation-associated pathology. For example, T_H17 cells trans-differentiate into T_H1-like T_H17 cells in an IL-23-dependent manner and drive tissue pathology in multiple sclerosis, inflammatory bowel disease, diabetes, and autoimmune arthritis. Similarly, uncommitted T_reg cells, characterized by low Foxp3 and CD25 expression, can convert into IL-17A-producing effector cells and upregulate RANKL expression, which increases their osteoclastogenic activity. Such T_H17-like T_reg cells not only lost their suppressive functions, but also accelerated arthritis pathology. Future studies should be focused to elaborate and functionally characterize transcription factors that regulate the generation and functional plasticity of pathogenic CD4⁺ T_H effector cells