| First Author | Mandarano AH | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 2 | Pages | 112106 |
| PubMed ID | 36773294 | Mgi Jnum | J:333452 |
| Mgi Id | MGI:7437245 | Doi | 10.1016/j.celrep.2023.112106 |
| Citation | Mandarano AH, et al. (2023) DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development. Cell Rep 42(2):112106 |
| abstractText | Drak2-deficient (Drak2(-/-)) mice are resistant to multiple models of autoimmunity yet effectively eliminate pathogens and tumors. Thus, DRAK2 represents a potential target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved. Here, we demonstrate that resistance to T1D in non-obese diabetic (NOD) mice is due to the absence of Drak2 in T cells and requires the presence of regulatory T cells (T(regs)). Contrary to previous hypotheses, we show that DRAK2 does not limit TCR signaling. Rather, DRAK2 regulates IL-2 signaling by inhibiting STAT5A phosphorylation. We further demonstrate that enhanced sensitivity to IL-2 in the absence of Drak2 augments thymic T(reg) development. Overall, our data indicate that DRAK2 contributes to autoimmunity in multiple ways by regulating thymic T(reg) development and by impacting the sensitivity of conventional T cells to T(reg)-mediated suppression. |
