title: The light and the dark sides of Interleukin-10 in immune-mediated diseases and cancer.
abstract: Interleukin-10 (IL-10) is known to be a tolerogenic cytokine since it inhibits pro-inflammatory cytokine production and T cell stimulatory capacities of myeloid cells, such as macrophages and dendritic cells. In particular, it has a non-redundant tolerogenic role in intestinal immune homeostasis, since mice and patients with genetic defects in the IL-10/IL-10R pathway develop spontaneously colitis in the presence of a normal intestinal flora. However, IL-10 is also a growth and differentiation factor for B-cells, can promote autoantibody production and has consequently a pathogenic role in systemic lupus erythematosus. Moreover, IL-10 can promote cytotoxic T-cell (CTL) responses and this immunogenic activity might be relevant in type-1 diabetes and anti-tumor immune responses. This review summarizes these paradoxic effects of IL-10 on different types of immune responses, and proposes that different cellular sources of IL-10, in particular IL-10-secreting helper and regulatory T-cells, have different effects on B-cell and CTL responses. Based on this concept we discuss the rationales for targeting the IL-10 pathway in immune-mediated diseases and cancer.
authors.affiliation: INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy. Electronic address: geginat@ingm.org.
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.affiliation: INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Larghi
authors.affiliation: INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Paroni
authors.affiliation: INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nizzoli
authors.affiliation: DISCCO, Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Penatti
authors.affiliation: INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA; Medical Department & Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.affiliation: DISCCO, Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Meroni
authors.affiliation: INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy; DISCCO, Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA; Howard Hughes Medical Institute, New Haven, Connecticut, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016753:Interleukin-10
keywords: Cancer; Colitis; Interleukin-10; Systemic lupus erythematosus; T-cells