Figure 1.

Abnormalities in the DNA damage repair pathway in T cells of rheumatoid arthritis patients. DNA stability is critical for the function of T cells. Naïve T cells from RA patients have ATM deficiency, which impairs the cells' ability to detect and repair DNA lesions. T cells alternatively upregulate DNA-PKcs. The activated DNA-PKcs-JNK-Bim axis eventually forces naïve T cells into apoptosis. Moreover, there is insufficient activation of the ATM kinase, hTERT, and MRE11A in RA-associated T cells after T cell receptor stimulation, which accelerates the G2/M checkpoint bypass and hyperproliferation. Unrepaired DNA breaks and telomere erosion finally induce T cell death and senescence. To compensate for the T cell pool, naive cells are forced into homeostatic clonal expansion, which facilitates the section of autoreactive T cell.