Figure 2.

A model depicting the DNA damage response pathway inducing disease-related phenotypes in T cells in rheumatoid arthritis. RA risk factors, including viral infection, environmental events, and genetic factors lead to defective DDR signals in T cells, and the inadequate DDR responsiveness subsequently alters T cell functionality in multiple aspects. First, deficiency in DNA repair influences T cell survival resulting in a lower apoptotic threshold. Second, DDR is implicated in the metabolic regulation of RA-associated T cells. Moreover, an impaired DDR response biases T cell differentiation to inflammatory effector T cells. Therefore, DDR deficiency in RA-associated T cells represents a key mechanism for the pathogenesis of RA with transitional genetic and environmental factors to RA pathogenesis-related T cell dysfunction.