| First Author | O'Hagan KL | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 4 | Pages | 1564-77 |
| PubMed ID | 26157175 | Mgi Jnum | J:260032 |
| Mgi Id | MGI:6150127 | Doi | 10.4049/jimmunol.1500843 |
| Citation | O'Hagan KL, et al. (2015) Pak2 Links TCR Signaling Strength to the Development of Regulatory T Cells and Maintains Peripheral Tolerance. J Immunol 195(4):1564-77 |
| abstractText | Although significant effort has been devoted to understanding the thymic development of Foxp3(+) regulatory T cells (Tregs), the precise signaling pathways that govern their lineage commitment still remain enigmatic. Our findings show a novel role for the actin cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), in Treg development and homeostasis. The absence of Pak2 in T cells resulted in a marked reduction in both thymus- and peripherally derived Tregs, accompanied by the development of spontaneous colitis in Pak2-deficient mice. Additionally, Pak2 was required for the proper differentiation of in vitro-induced Tregs as well as maintenance of Tregs. Interestingly, Pak2 was necessary for generating the high-affinity TCR- and IL-2-mediated signals that are required by developing Tregs for their lineage commitment. These findings provide novel insight into how developing thymocytes translate lineage-specific high-affinity TCR signals to adopt the Treg fate, and they further posit Pak2 as an essential regulator for this process. |
