title: IL-27 in human secondary lymphoid organs attracts myeloid dendritic cells and impairs HLA class I-restricted antigen presentation.
abstract: Different cytokines play crucial roles in inflammation and in polarizing immune responses, including IL-27 that exerts pro- and anti-inflammatory functions. Although the activity of IL-27 is well characterized in murine immune cells, only limited information is available regarding the natural cellular sources of IL-27 in humans and its effects on human immune cells. Dendritic cells (DCs) are the most potent professional APCs that in the immature state are positioned throughout peripheral tissues by acting as sentinels, sensing the presence of Ags. Activated DCs migrate into the lymph nodes and direct Ag-specific T cell responses, thus acting as key players in both adaptive and innate immunity. In this study we asked whether IL-27 is produced by human secondary lymphoid organs and what is its functional role on human DCs. To our knowledge, we provide the first evidence that 1) in lymph nodes, macrophages are the major source for IL-27; 2) immature and mature human DCs express functional IL-27R; 3) IL-27 exerts immunosuppressive activity by crippling the Ag processing machinery in immature DCs under steady-state conditions and after pulsing with a viral Ag; and 4) IL-27 is chemotactic for human DCs. Our findings highlight novel mechanisms underlying the immunosuppressive activity of IL-27, suggesting that this cytokine may function as a homeostatic cytokine in secondary lymphoid organs by limiting duration and/or intensity of ongoing adaptive immune responses. The results presented in this study pave the way to future studies aimed at investigating whether dysregulation of IL-27 expression and function may be involved in pathogenesis of autoimmune disease and cancer.
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, 16147 Genoa, Italy;
authors.forename: Fabio
authors.initials: F
authors.lastname: Morandi
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.forename: Irma
authors.initials: I
authors.lastname: Airoldi
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D064094:Interleukin-27 / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; D019309:Epstein-Barr Virus Nuclear Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D064094:Interleukin-27; D018123:Receptors, Interleukin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C112441:IL27RA protein, human; C417029:EBV-encoded nuclear antigen 1