First Author | Sokol CL | Year | 2018 |
Journal | Immunity | Volume | 49 |
Issue | 3 | Pages | 449-463.e6 |
PubMed ID | 30170811 | Mgi Jnum | J:277044 |
Mgi Id | MGI:6284468 | Doi | 10.1016/j.immuni.2018.07.012 |
Citation | Sokol CL, et al. (2018) The Chemokine Receptor CCR8 Promotes the Migration of Dendritic Cells into the Lymph Node Parenchyma to Initiate the Allergic Immune Response. Immunity 49(3):449-463.e6 |
abstractText | The migration of mature dendritic cells (DCs) into the draining lymph node (dLN) is thought to depend solely on the chemokine receptor CCR7. CD301b(+) DCs migrate into the dLN after cutaneous allergen exposure and are required for T helper 2 (Th2) differentiation. We found that CD301b(+) DCs poorly upregulated CCR7 expression after allergen exposure and required a second chemokine signal, mediated by CCR8 on CD301b(+) DCs and its ligand CCL8, to exit the subcapsular sinus (SCS) and enter the lymph node (LN) parenchyma. After allergen exposure, CD169(+)SIGN-R1(+) macrophages in interfollicular regions produced CCL8, which synergized with CCL21 in a Src-kinase-dependent manner to promote CD301b(+) DC migration. In CCR8-deficient mice, CD301b(+) DCs remained in the SCS and were unable to enter the LN parenchyma, resulting in defective Th2 differentiation. We have defined a CCR8-dependent stepwise mechanism of DC-subset-specific migration through which LN CD169(+)SIGN-R1(+) macrophages control the polarization of the adaptive immune response. |