title: Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function.
abstract: The most prevalent cancer diagnosed in the world is sunlight-induced skin cancer. In addition to being a complete carcinogen, UV radiation, the causative agent of skin cancer, induces immune suppression. Because UV-induced immune suppression is a well-recognized risk factor for skin cancer induction, it is crucial to understand the mechanisms underlying UV-induced immune suppression. Mast cells, which have recently emerged as immune regulatory cells, are particularly important in UV-induced immune suppression. UV exposure does not induce immune suppression in mast cell-deficient mice. We report that UV irradiation blocks germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell function, in part by altering the expression of transcription factors BCL-6 and BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab secretion was observed in UV-irradiated mast cell-deficient (Kit(W-sh/W-sh)) mice. When mast cell-deficient mice were reconstituted with wild type mast cells, immune suppression was restored. Reconstituting the mast cell-deficient mice with bone marrow-derived mast cells from IL-10-deficient mice failed to restore the ability of UV radiation to suppress GC formation. Our findings demonstrate a function for mast cells, suppression of Tfh cell production, GC formation, and Ab production in vivo.
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rommel
authors.initials: R
authors.lastname: Chacón-Salinas
authors.forename: Alberto Y
authors.initials: AY
authors.lastname: Limón-Flores
authors.forename: Alma D
authors.initials: AD
authors.lastname: Chávez-Blanco
authors.forename: Alexei
authors.initials: A
authors.lastname: Gonzalez-Estrada
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology* / Q000528:radiation effects; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology* / Q000528:radiation effects; D006131:Growth Inhibitors / Q000502:physiology*; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000528:radiation effects; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D000098546:Interleukin-21
chemical_list: D006131:Growth Inhibitors; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D016753:Interleukin-10; D019009:Proto-Oncogene Proteins c-kit; D000098546:Interleukin-21