Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity

J Allergy Clin Immunol. 2012 Dec;130(6):1384-93. doi: 10.1016/j.jaci.2012.08.039. Epub 2012 Oct 24.


Background: IL-10-treated dendritic cells (DCs) have been shown to inhibit T-cell responses through induction of anergy and regulatory T cells in various model systems, including allergic inflammation, but the factors being involved in this inhibition are still unclear.

Objective: This study set out to analyze such factors produced or induced by IL-10-treated DCs by using gene expression profiling and to explore their function.

Methods: CD4(+) T cells from allergic donors were stimulated with autologous monocyte-derived allergen-pulsed mature DCs or IL-10-treated DCs. After 24 hours, the transcriptional profile was analyzed by using Affymetrix technology. Results were validated by using quantitative real-time PCR, protein expression, and functional in vitro and in vivo studies.

Results: In CD4(+) T-cell/IL-10-treated DC cocultures the expression of several known genes, such as IL13, IL5 and OX40, was suppressed. Interestingly, there was only one factor that was strongly upregulated: the DC-derived chemokine CCL18. In vitro addition of CCL18 to cocultures of CD4(+) T cells and allergen-pulsed DCs resulted in a similar inhibition of T(H)2 cytokine production as induced by allergen-pulsed IL-10-treated DCs without exogenous CCL18, whereas T(H)1 cytokine production, IL-10 production, and proliferation were not affected. Furthermore, in a humanized mouse model of allergy using PBMC-engrafted NOD-scid-γc(-/-) mice, CCL18, but not another T(H)2-associated chemokine, CCL17, inhibited airway reactivity and lung inflammation. Chemotaxis assays revealed that CCL18 preferentially attracted regulatory T cells and, less efficiently, T(H)2 cells.

Conclusion: These data demonstrate that CCL18 might represent a molecule of significant importance in immunoregulation and might be a therapeutic target in patients with allergic airway diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Chemokines, CC / immunology*
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Disease Models, Animal
  • Humans
  • Immune Tolerance
  • Interleukin-10 / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Microarray Analysis
  • Respiratory Hypersensitivity / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Transcriptome


  • CCL18 protein, human
  • Chemokines, CC
  • Interleukin-10