Successful granulocyte-colony stimulating factor treatment of Crohn's disease is associated with the appearance of circulating interleukin-10- producing T cells and increased lamina propria plasmacytoid dendritic cells

P. J. Mannon, F. Leon, I. J. Fuss, B. A. Walter, M. Begnami, M. Quezado, Z. Yang, C. Yi, C. Groden, J. Friend, R. L. Hornung, M. Brown, S. Gurprasad, B. Kelsall, W. Strober

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 μg/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4+ memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123+ plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-γ production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa.

Original languageEnglish (US)
Pages (from-to)447-456
Number of pages10
JournalClinical and Experimental Immunology
Volume155
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Cytokines
  • FoxP2
  • Plasmacytoid dendritic cells
  • Regulatory T cells
  • Th1 inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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