Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function

• Published in: The Journal of immunology (1950) 2011-01, Vol.186 (1), p.25-31
• Main Authors: Chacón-Salinas, Rommel, Limón-Flores, Alberto Y, Chávez-Blanco, Alma D, Gonzalez-Estrada, Alexei, Ullrich, Stephen E
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation - radiation effects; Bone Marrow Transplantation - immunology; Cell Differentiation - immunology; Cell Differentiation - radiation effects; Germinal Center - cytology; Germinal Center - immunology; Germinal Center - radiation effects; Growth Inhibitors - physiology; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - physiology; Interleukins - antagonists & inhibitors; Interleukins - biosynthesis; Interleukins - radiation effects; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mast Cells - immunology; Mast Cells - metabolism; Mast Cells - transplantation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Proto-Oncogene Proteins c-bcl-6 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-6 - biosynthesis; Proto-Oncogene Proteins c-bcl-6 - radiation effects; Proto-Oncogene Proteins c-kit - genetics; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - radiation effects; Ultraviolet Rays
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001657

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.