Type I interferons attenuate T cell activating functions of human mast cells by decreasing TNF-alpha production and OX40 ligand expression while increasing IL-10 production.
Recent studies have demonstrated that mast cells not only mediate inflammatory reactions in type I allergy but also play an important role in adaptive immunity. In the present study, we investigated the effects of interferon-alpha, which shares the same receptor as IFN-beta, on human cord blood-derived mast cells. Mast cells produced TNF-alpha, and IL-10, and expressed OX40 ligand upon activation by crosslinking of FcepsilonRI. When treated with interferon-alpha, TNF-alpha production was decreased while IL-10 and TGF-beta productions were increased. Furthermore, flow cytometric analysis revealed that interferon-alpha downregulated expression OX40 ligand on mast cells which is crucial for mast cell-T cell interaction. We confirmed that the viability of mast cells was not affected by interferon-alpha treatment. Accordingly, interferon-alpha-treated mast cells induced lower levels of CD4+ T cell proliferation compared with those without interferon-alpha treatment. These results suggest that type I interferons suppress T cell immune responses through their regulatory effects on mast cells.
Fujita
Tomoko
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Kambe
Naotomo
N
Uchiyama
Takashi
T
Hori
Toshiyuki
T
D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D053278:OX40 Ligand / Q000096:biosynthesis*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007166:Immunosuppressive Agents; D007370:Interferon Type I; D053278:OX40 Ligand; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10