Phenotypic and functional differences between wild-type and CCR2 -/- dendritic cells: Implications for islet transplantation

Paolo Fiorina, Mollie Jurewicz, Andrea Vergani, Andrea Augello, Jesus Paez, Vincent Ricchiuti, Vaja Tchipachvili, Mohamed H. Sayegh, Reza Abdi

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. Trafficking of dendritic cells (DC), the primary regulators of alloimmune responses, is controlled by chemokines. Here, we provide evidence that lack of CCR2 could lead to the generation of functionally and phenotypically different DC, which in part could explain the benefits observed in transplanting islets in CCR2 recipients. METHODS AND RESULTS. We show that, in contrast to the in vitro DC maturation model, in vivo DC maturation is accompanied by an increase in the expression of CCR2. Compared with wild-type (WT), DC generated in vitro from CCR2 mice, and DC extracted from CCR2 naïve mice or from CCR2 recipients of islet allografts, display lesser allostimulatory capacity. Compared with WT DC, CCR2 DC produce more IL-4 and induce more IL-4-producing T cells. CCR2 DC also promote the generation of regulatory T cells that more efficiently suppress T cell proliferative responses by mixed leukocyte reaction. Similarly, the percentage of CD4CD25FoxP3 cells were found to be higher in CCR2 recipients of islet allografts than in WT recipients. CONCLUSIONS. In summary, lack of CCR2 interferes with the allostimulatory capacity of DC and promotes the generation of regulatory T cells. This is the first demonstration of a mechanistic link between targeting a specific chemokine pathway and the DC-regulatory T cell axis in alloimmunity.

Original languageEnglish
Pages (from-to)1030-1038
Number of pages9
JournalTransplantation
Volume85
Issue number7
DOIs
Publication statusPublished - Apr 2008

Keywords

  • Chemokines
  • Dendritic cells
  • Islet transplantation
  • Regulatory cells
  • Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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