Figure 4. FXII controls cytokine production via CD87.

(a) Splenic cDCs from naive WT animals were stimulated with 1 μg ml⁻¹ LPS in the absence and presence of 60 nM activated FXII (FXIIa). After 48 h, cytokine concentrations were measured in culture supernatants by ELISA. (b) Cytokine production of splenic cDCs from WT animals stimulated with 1 μg ml⁻¹ LPS in the absence and presence of 60 nM non-cleavable FXII. After 48 h, cytokine concentrations were determined in culture supernatants by ELISA. (c) Cytokine production of splenic cDCs from CD87-deficient (Cd87^−/−) mice stimulated with 1 μg ml⁻¹ LPS alone or in the absence and presence of 60 nM FXII for 48 h. (d) Cytokine production of splenic cDCs from CD11b-deficient (Itgam^−/−) animals stimulated with 1 μg ml⁻¹ LPS in the absence and presence of 60 nM FXII for 48 h. (e) Cytosolic cAMP formation measured in cDCs from WT or Cd87^−/− mice that were incubated with medium only (Ctrl) or stimulated with 1 μg ml⁻¹ LPS for 10 min in the absence (Ctrl) or presence of 60 nM FXII. (f) Cytokine concentrations of IL-6 (left panel) and IL-23 (right panel) in the supernatants of WT cDCs stimulated with 1 μg ml⁻¹ LPS or 60 nM FXII for 48 h in the presence of protein kinase A inhibitors (3 μM H-89 and 100 μM Rp-8-Br-cAMP). (g) Cytokine concentrations of IFN-γ, IL-17A, IL-6, IL-12 and IL-23 were measured in the supernatants from co-cultures of CD4⁺ T lymphocytes from WT (upper panel) or Cd87^−/− (lower panel) that were polyclonal activated together with cDCs from WT and Cd87^−/− in the absence or presence of 60 nM FXII. In a–g, data are given as means±s.e.m. of three independent experiments, each performed in duplicate (non-parametric Mann–Whitney U-test). *P<0.05, **P<0.01, ***P<0.001; NS, not significant.