Claudin-5 haploinsufficiency exacerbates UVB-induced oedema formation by inducing lymphatic vessel leakage

Acute exposure of skin to ultraviolet (UV) B irradiation (290320 similar to nm) leads to epidermal hyperplasia, erythema and oedema formation. We have elucidated that UV irradiation induced the leakiness of cutaneous lymphatic vessels. Although these studies indicated a crucial role of the lymphatic integrity in skin inflammation, the mechanisms underlying its disruption by UVB exposure remain unknown. Here we demonstrated that a vascular-specific tight junction molecule, claudin-5 has an important role in lymphatics and skin inflammation. Claudin-5+/- mice, whose claudin-5 expression was greatly downregulated in skin, exacerbates oedema formation and inflammation by a low dose of UVB irradiation. Lymphatic vessels of claudin-5+/- mice were markedly enlarged and leaky after low-dose UVB exposure, compared with those of wild-type mice, while the morphology of blood vessels were not different between groups. These results suggest that claudin-5 in the lymphatic tight junction maintains lymphatic integrity and plays a protective role in skin inflammation.