CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes

J Exp Med. 2019 May 6;216(5):1170-1181. doi: 10.1084/jem.20170277. Epub 2019 Mar 25.


Chemokines have crucial roles in organ development and orchestration of leukocyte migration. The chemokine CCL22 is expressed constitutively at high levels in the lymph node, but the functional significance of this expression is so far unknown. Studying a newly established CCL22-deficient mouse, we demonstrate that CCL22 expression by dendritic cells (DCs) promotes the formation of cell-cell contacts and interaction with regulatory T cells (T reg) through their CCR4 receptor. Vaccination of CCL22-deficient mice led to excessive T cell responses that were also observed when wild-type mice were vaccinated using CCL22-deficient DCs. Tumor-bearing mice with CCL22 deficiency showed prolonged survival upon vaccination, and further, CCL22-deficient mice had increased susceptibility to inflammatory disease. In conclusion, we identify the CCL22-CCR4 axis as an immune checkpoint that is crucial for the control of T cell immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology*
  • Cell Communication / immunology*
  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CCL22 / genetics
  • Chemokine CCL22 / immunology*
  • Dendritic Cells / immunology*
  • HEK293 Cells
  • Humans
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR4 / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Transplantation, Homologous


  • Ccl22 protein, mouse
  • Chemokine CCL22
  • Receptors, CCR4