| First Author | Matsumura F | Year | 2021 |
| Journal | J Immunol | Volume | 207 |
| Issue | 3 | Pages | 938-949 |
| PubMed ID | 34301846 | Mgi Jnum | J:311390 |
| Mgi Id | MGI:6766085 | Doi | 10.4049/jimmunol.2000318 |
| Citation | Matsumura F, et al. (2021) Investigation of Fascin1, a Marker of Mature Dendritic Cells, Reveals a New Role for IL-6 Signaling in CCR7-Mediated Chemotaxis. J Immunol 207(3):938-949 |
| abstractText | Migration of mature dendritic cells (DCs) to lymph nodes is critical for the initiation of adaptive immunity. CCR7, a G-protein-coupled receptor for CCL19/21 chemokines, is known to be essential for chemotaxis of mature DCs, but the molecular mechanism linking inflammation to chemotaxis remains unclear. We previously demonstrated that fascin1, an actin-bundling protein, increases chemotaxis of mature mouse DCs. In this article, we demonstrated that fascin1 enhanced IL-6 secretion and signaling of mature mouse DCs. Furthermore, we demonstrated that IL-6 signaling is required for chemotaxis. Blockage of IL-6 signaling in wild-type DCs with an anti-IL-6 receptor alpha (IL-6Ralpha) Ab inhibited chemotaxis toward CCL19. Likewise, knockout of IL-6Ralpha inhibited chemotaxis of bone marrow-derived DCs. The addition of soluble IL-6Ralpha and IL-6 rescued chemotaxis of IL-6Ralpha knockout bone marrow-derived DCs, underscoring the role of IL-6 signaling in chemotaxis. We found that IL-6 signaling is required for internalization of CCR7, the initial step of CCR7 recycling. CCR7 recycling is essential for CCR7-mediated chemotaxis, explaining why IL-6 signaling is required for chemotaxis of mature DCs. Our results have identified IL-6 signaling as a new regulatory pathway for CCR7/CCL19-mediated chemotaxis and suggest that rapid migration of mature DCs to lymph nodes depends on inflammation-associated IL-6 signaling. |
