title: Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling.
abstract: 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.
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: C E
authors.initials: CE
authors.lastname: Matisz
authors.affiliation: Unidad de Biomedicina, FES Iztacala, Universidad Nacional Autónoma de México, Estado de México, México.
authors.forename: B
authors.initials: B
authors.lastname: Faz-López
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Thomson
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Al Rajabi
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Lopes
authors.affiliation: Unidad de Biomedicina, FES Iztacala, Universidad Nacional Autónoma de México, Estado de México, México.
authors.forename: L I
authors.initials: LI
authors.lastname: Terrazas
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Sharkey
authors.affiliation: Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: D M
authors.initials: DM
authors.lastname: McKay
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015415:Biomarkers; D003092:Colitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D055786:Gene Knockout Techniques; D048190:Hymenolepis diminuta / Q000276:immunology; D007150:Immunohistochemistry; D056747:Immunomodulation; D016130:Immunophenotyping; D007167:Immunotherapy; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D015415:Biomarkers; D053662:Interleukin-4 Receptor alpha Subunit; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015847:Interleukin-4