Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling

Sci Rep. 2017 Jan 17;7:40631. doi: 10.1038/srep40631.


Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling. Transfer of HD-DCs suppressed dinitrobenzene sulfonic acid (DNBS)-induced colitis through activation of recipient IL-4 receptor-α. The transferred HD-DCs required IL-4Rα and the capacity to secrete IL-10 to drive IL-4 and IL-10 production and to suppress colitis in recipient mice. Treatment of DCs with IL-4 evokes an alternatively activated phenotype, but adoptive transfer of these cells did not affect the outcome of colitis. Collectively, these studies demonstrate the complexity between IL-4 and IL-10 in donor cells and recipient, and the requirement for parasite- and host-derived factors in this novel form of cell therapy. Thus IL-4Rα signaling is revealed as a pathway that could be exploited for helminth antigen cell-based therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Helminth / immunology*
  • Biomarkers
  • Colitis / etiology*
  • Colitis / metabolism*
  • Colitis / pathology
  • Colitis / therapy
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Gene Knockout Techniques
  • Hymenolepis diminuta / immunology
  • Immunohistochemistry
  • Immunomodulation
  • Immunophenotyping
  • Immunotherapy
  • Interleukin-10 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukin-4 Receptor alpha Subunit / metabolism*
  • Lipopolysaccharides / immunology
  • Mice
  • Signal Transduction*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism


  • Antigens, Helminth
  • Biomarkers
  • Interleukin-4 Receptor alpha Subunit
  • Lipopolysaccharides
  • Interleukin-10
  • Interleukin-4

Grant support