| First Author | Ishimaru N | Year | 2012 |
| Journal | Am J Pathol | Volume | 180 |
| Issue | 1 | Pages | 199-208 |
| PubMed ID | 22067914 | Mgi Jnum | J:180162 |
| Mgi Id | MGI:5305539 | Doi | 10.1016/j.ajpath.2011.09.027 |
| Citation | Ishimaru N, et al. (2012) CCR7 with S1P1 signaling through AP-1 for migration of Foxp3+ regulatory T-cells controls autoimmune exocrinopathy. Am J Pathol 180(1):199-208 |
| abstractText | Forkhead box p3-positive (Foxp3(+)) regulatory T cells (T(reg) cells) participate in maintaining peripheral immune tolerance and suppressing autoimmunity. We recently reported that in situ patrolling by C-C-chemokine receptor 7 (CCR7)(+) T(reg) cells in target organs is essential for controlling autoimmune lesions in Sjogren's syndrome. In the present study, the molecular mechanism underlying CCR7-mediated T(reg) cell migration was investigated in a mouse model. The impaired migratory response of Ccr7(-/-) T(reg) cells to sphingosine 1-phosphate (S1P) occurred because of defective association of S1P receptor 1 (S1P(1)) with a G coupled-protein. In addition, T-cell receptor (TCR)- and S1P(1)-mediated Ras-related C3 botulinum toxin substrate 1 (Rac-1), extracellular signal-related kinase (ERK), and c-Jun phosphorylation required for activator protein 1 (AP-1) transcriptional activity were significantly impaired in Ccr7(-/-) T(reg) cells. Surprisingly, the abnormal nuclear localization of Foxp3 was detected after abrogation of the c-Jun and Foxp3 interaction in the nucleus of Ccr7(-/-) T(reg) cells. These results indicate that CCR7 essentially controls the migratory function of T(reg) cells through S1P(1)-mediated AP-1 signaling, which is regulated through its interaction with Foxp3 in the nucleus. |
