Fig. 6.

BLT1^lo DCs preferentially induce T cell proliferation by producing IL-2. a, b BLT1^hi and BLT1^lo DCs were treated with CpG DNA (500 nM) for 4 h and 24 h, followed by QPCR and CBA analyses for IL-2, respectively. c CD4+ T cells were cultured for 3 days with a recombinant IL-2 protein (10 ng/ml) or vehicle (CON), and cell numbers were counted. CD4+ T cells derived from the OT-II Tg spleen were stained with CMFDA and cocultured for 3 days (d, e) and 2 days (f) with either BLT1^hi or BLT1^lo DCs in the presence of an OVA peptide. Proliferating CD4+ T cells were analyzed by flow cytometric analysis (n = 3; error bars indicate the S.E.M.). A neutralizing antibody against murine IL-2 was added to the coculture system in f (10 μg/ml). A rat IgG2a kappa isotype control antibody was added to the control group. g, h BLT1^hi and BLT1^lo DCs were loaded with the OVA peptide (1 μg/ml) for 16 h and injected intravenously into OT-II Tg mice. CpG DNA was also injected intraperitoneally. At three days post-DC transfer, spleen size and splenocyte number were evaluated (n = 2; error bars indicate the S.E.M.). *P < 0.05; **P < 0.01; ***P < 0.001; unpaired Student’s t-test (c, e, g); one-way ANOVA with Bonferroni’s post hoc test (a, b). i The schematic model shows how the novel BLT1^hi and BLT1^lo DC subsets control skin inflammation. There are two DC subsets, BLT1^hi and BLT1^lo DCs, in peripheral tissues. BLT1^lo DCs migrate preferentially toward draining lymph nodes and produce high amounts of IL-2 to induce T cell proliferation. On the other hand, BLT1^hi DCs migrate toward LTB₄, which is produced by inflammatory cells, such as neutrophils, in inflammatory areas. BLT1^hi DCs produce large amounts of IL-12, which boosts Th1 differentiation. Expanded differentiated Th1 cells produce IFN-γ, which drives spongiosis and edema in inflamed peripheral tissues