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

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

Author information

1
Center of Integrated Protein Science Munich, Division of Clinical Pharmacology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
2
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
3
Department of Immunology, Harvard Medical School, Boston, MA.
4
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
5
Department of Anaesthetics, Pharmacology, Intensive Care and Emergencies, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
6
Department of Immunology, Harvard Medical School, Boston, MA uva@hms.harvard.edu.
7
The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
8
Center of Integrated Protein Science Munich, Division of Clinical Pharmacology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany endres@lmu.de.
9
German Cancer Consortium (DKTK), partner site Munich, Munich, Germany.
10
Department of Medicine II, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Abstract

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.

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