C5a drives Th17 cell differentiation and triggers arthritis. (A) Joint score of C5aR+/+ or C5aR−/− SKG mice treated by 20 mg mannan. A total of two independent experiments are shown. Error bars are means ± SD of scores. *, P < 0.05. (B) Spleen and popliteal lymph nodes of C5aR+/+ or C5aR−/− SKG mice 8 wk after mannan treatment. (C) Intracellular staining of IL-17 and IFN-γ in CD4+ T cells in the popliteal lymph nodes of C5aR+/+ or C5aR −/− SKG mice, as shown in B (numbers indicate percentages). One representative staining out of nine independent experiments is shown. (D and E) Percentages (D) and absolute numbers (E) of IL-17+ cells in CD4+ T cells in each group (n = 9), as shown in C. (F) Joint scores of C5aR+/+ or C5aR−/− SKG mice 8 wk after treatment by laminarin (n = 7) or zymosan (n = 6). (G) C3 deposition assay with laminarin-, zymosan-, or mannan-coated wells incubated with 2% sera from MASP-intact or -null C57BL/6 sera. (H) C5a ELISA for the supernatant of the C3 deposition assay with BALB/c sera, as shown in G. Error bars are means ± SD. (I) C5aR+/+ and C5aR−/− SKG mice were i.p. injected with TNP-BSA alone or IgG3 anti-TNP/TNP-BSA IC. The percentage of IL-17+ cells in the peritoneal CD4+ T cells was assessed on day 7 (n = 4). Horizontal bars are the means.