Figure 7: Loss of PLCδ1 in keratinocytes exaggerates CHS responses.

(a) Time course of ear swelling after DNFB challenge. Ear swelling was measured at the indicated times. Mean±s.d. (n=4). (b) HE stains of ear after DNFB challenge. The ears of sensitized mice were painted with DNFB, collected 96 h later and stained with HE. Lower panels are magnified views of the boxed regions in the upper panels. Scale bar in upper panel, 100 μm. Scale bar in lower panel,50 μm. (c) Sensitized mice were treated with anti-IL-17 neutralizing antibody or normal rat IgG before challenge, and ear swelling was measured at the indicated times. Mean±s.d. (n=3). Mice used in all experiments were 8–12 weeks old. The data presented in (b) are representative of three mice per genotype. Statistical significance was assessed using a Student′s t-test. **P<0.01. (d) Proposed model of local and systemic phenotypes induced by epidermal loss of PLCδ1. Epidermal loss of PLCδ1 impairs overall PLC activity and activation of PLC downstream signals, which causes increased production of IL-23 in the epidermis and whole skin. IL-23 induces IL-17 production in the epidermis. IL-17 was also overproduced in the skin-draining lymph nodes. This aberrant activation of the local IL-23/IL-17 axis resulted in a phenotype similar to that in human psoriasis and exaggerated CHS responses. Regarding systemic phenotypes, serum IL-17 levels were increased presumably as a result of skin and/or skin-draining lymph node-derived IL-17 (dotted arrow). Elevated serum IL-17 concentrations likely cause subsequent granulocytosis through G-CSF production (dotted arrow).