OBJECTIVE: Tolerogenic dendritic cells (DCs) are antigen-presenting cells with an immunosuppressive function. They are a promising immunotherapeutic tool for the attenuation of pathogenic T cell responses in autoimmune arthritis. The aims of this study were to determine the therapeutic action of tolerogenic DCs in a type II collagen-induced arthritis model and to investigate their effects on Th17 cells and other T cell subsets in mice with established arthritis. METHODS: Tolerogenic DCs were generated by treating bone marrow-derived DCs with dexamethasone and vitamin D(3) during lipopolysaccharide-induced maturation. Mice with established arthritis received 3 intravenous injections of tolerogenic DCs, mature DCs, or saline. Arthritis severity was monitored for up to 4 weeks after treatment. Fluorescence-labeled tolerogenic DCs were used for in vivo trafficking studies. The in vivo effect of tolerogenic DCs on splenic T cell populations was determined by intracellular cytokine staining and flow cytometry. RESULTS: Tolerogenic DCs displayed a semi-mature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4+ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing γ/δ T cells. CONCLUSION: Treatment with type II collagen-pulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.
OBJECTIVE: Tolerogenic dendritic cells (DCs) are antigen-presenting cells with an immunosuppressive function. They are a promising immunotherapeutic tool for the attenuation of pathogenic T cell responses in autoimmune arthritis. The aims of this study were to determine the therapeutic action of tolerogenic DCs in a type II collagen-induced arthritis model and to investigate their effects on Th17 cells and other T cell subsets in mice with established arthritis. METHODS: Tolerogenic DCs were generated by treating bone marrow-derived DCs with dexamethasone and vitamin D(3) during lipopolysaccharide-induced maturation. Mice with established arthritis received 3 intravenous injections of tolerogenic DCs, mature DCs, or saline. Arthritis severity was monitored for up to 4 weeks after treatment. Fluorescence-labeled tolerogenic DCs were used for in vivo trafficking studies. The in vivo effect of tolerogenic DCs on splenic T cell populations was determined by intracellular cytokine staining and flow cytometry. RESULTS: Tolerogenic DCs displayed a semi-mature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4+ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing γ/δ T cells. CONCLUSION: Treatment with type II collagen-pulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.
Authors: Raquel Cabezón; E Antonio Carrera-Silva; Georgina Flórez-Grau; Andrea E Errasti; Elisabeth Calderón-Gómez; Juan José Lozano; Carolina España; Elena Ricart; Julián Panés; Carla Vanina Rothlin; Daniel Benítez-Ribas Journal: J Leukoc Biol Date: 2015-01-26 Impact factor: 4.962
Authors: Manon A A Jansen; Rachel Spiering; Femke Broere; Jacob M van Laar; John D Isaacs; Willem van Eden; Catharien M U Hilkens Journal: Immunology Date: 2017-09-18 Impact factor: 7.397
Authors: M B Ezzelarab; D Raich-Regue; L Lu; A F Zahorchak; A Perez-Gutierrez; A Humar; M Wijkstrom; M Minervini; R W Wiseman; D K C Cooper; A E Morelli; A W Thomson Journal: Am J Transplant Date: 2017-02-02 Impact factor: 8.086
Authors: Jeroen N Stoop; Christopher A Tibbitt; Willem van Eden; John H Robinson; Catharien M U Hilkens Journal: Immunology Date: 2013-01 Impact factor: 7.397