A-E, WT C57BL/6 mice were sensitized with 3% OXA on abdominal skin on (day 0) and then challenged with 0.6% OXA or EtOH on ears 5 days later. Challenge with OXA was repeated once every two days for a total of 5 challenges. Ears and ear-draining LNs were collected 6 h after the last OXA challenge (n=4-5). A, Schematic representation of the experimental protocol. B, Ear thickness. C, Ear histology. Scale bar, 50 μM. D, CD4+ and CD8+ T cells in ear-draining LNs. E, IL-22 production by ear-draining LN cells cultured with soluble anti-CD3 or medium only in vitro for 3 days. F, Swelling of ears from control and EP4cKO mice (n=9-13) sensitized and repeatedly challenged with OXA as in A but without indomethacin treatment. *P<0.05; ***P<0.001 and ****P<0.0001.