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IL-20 receptor 2 signaling down-regulates antigen-specific T cell responses Wahl C; Muller W; Leithauser F; Adler G; Oswald F; Reimann J; Schirmbeck R; Seier A; Weiss JM; Prochnow B; Wegenka UMJ Immunol 2009[Jan]; 182 (2): 802-10The recently described cytokines IL-19, IL-20, and IL-24 share structural homology with IL-10 and are therefore classified as members of the IL-10 family of cytokines. Although it has long been speculated that signaling by their heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2) influences immunological processes, the target cells for this group of cytokines are still unclear. By generating a knockout mouse strain deficient for the common IL-20R beta-chain (IL-20R2), we show that IFN-gamma and IL-2 secretion is significantly elevated after stimulation of IL-20R2-/--deficient CD8 and CD4 T cells with Con A or anti-CD3/CD28 in vitro. IL-10 secretion by activated IL-20R2-/- CD4 cells was diminished. Consistent with our in vitro results, significantly more Ag-specific CD8 IFN-gamma+ and CD4 IFN-gamma+ T cells developed to locally applied DNA vaccines in IL-20R2-deficient mice. In a T cell-dependent model of contact hypersensitivity, IL-20R2 knockout mice were more sensitive to the contact allergen trinitro-chloro-benzene. Thus, IL-20R2 signaling directly regulates CD8 and CD4 T cell answers in vitro and in vivo. For the first time, we provide evidence that IL-19, IL-20, and IL-24 are part of a signaling network that normally down-modulates T cell responses in mice.|Allergens/administration & dosage/immunology[MESH]|Animals[MESH]|CD4-Positive T-Lymphocytes/*immunology/*metabolism[MESH]|CD8-Positive T-Lymphocytes/*immunology/*metabolism[MESH]|Cells, Cultured[MESH]|Coculture Techniques[MESH]|Dermatitis, Contact/genetics/immunology[MESH]|Down-Regulation/genetics/*immunology[MESH]|Epitopes, T-Lymphocyte/*immunology[MESH]|Female[MESH]|Lymphocyte Activation/immunology[MESH]|Mice[MESH]|Mice, Inbred BALB C[MESH]|Mice, Inbred C57BL[MESH]|Mice, Knockout[MESH]|Mice, Transgenic[MESH]|Picryl Chloride/administration & dosage/immunology[MESH]|Receptors, Interleukin/deficiency/genetics/*physiology[MESH]|Signal Transduction/genetics/*immunology[MESH]|Vaccines, DNA/administration & dosage/immunology[MESH] |
