The Chemokine Receptor CCR8 Promotes the Migration of Dendritic Cells into the Lymph Node Parenchyma to Initiate the Allergic Immune Response

Immunity. 2018 Sep 18;49(3):449-463.e6. doi: 10.1016/j.immuni.2018.07.012. Epub 2018 Aug 28.


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.

Keywords: CCL8; CCR8; Th2 differentiation; allergy; chemokines; dendritic cells; lymph node; macrophages; migration; papain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Movement
  • Cells, Cultured
  • Chemokine CCL8 / metabolism
  • Dendritic Cells / physiology*
  • Disease Models, Animal
  • Female
  • Hypersensitivity / immunology*
  • Integrin alpha Chains / metabolism
  • Lymph Nodes / immunology*
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR7 / metabolism*
  • Receptors, CCR8 / genetics
  • Receptors, CCR8 / metabolism*


  • Antigens, CD
  • Ccr7 protein, mouse
  • Ccr8 protein, mouse
  • Chemokine CCL8
  • Integrin alpha Chains
  • Receptors, CCR7
  • Receptors, CCR8
  • alpha E integrins