Background The lymphatic system is composed of vessels which carry fluid, soluble molecules, and cells from peripheral tissue to draining lymph nodes. Photosensitivity, an exaggerated inflammatory response in response to ultraviolet radiation (UVR), is present in most patients with Systemic Lupus Erythematosus (SLE). Lymphatic dysfunction has been shown to induce photosensitivity in wild-type models, thus we hypothesized that lymphatic dysfunction could contribute to photosensitivity in SLE.
Methods We examined MRL/lpr lupus prone mice for lymphatic function by injecting Evan’s Blue into the ear and measuring retention. Ear thickness and flow cytometric analysis were used to assess photosensitivity. Lymphatic drainage was manipulated using two approaches. First, we used manual lymphatic drainage (MLD) in the MRL/lpr mice. MLD improved lymphatic drainage and reduced photosensitivity. Second, we induced a lupus phenotype in a novel mouse model with enhanced lymphatic function (inducible lymphatic endothelial cell specific PTEN KO) using topical imiquimod.
Results MRL/lpr mice had greater Evan’s blue retention compared to controls suggesting lupus prone mice have impaired lymphatic drainage. MLD improved lymphatic drainage and reduced photosensitivity. PTEN KO mice had reduced photosensitivity and reduced systemic immune activation.
Conclusions This data suggests that lymphatic dysfunction contributes to photosensitivity in murine lupus and improving lymphatic flow, even with simple MLD, can ameliorate photosensitivity. Future studies will determine the etiology of lymphatic dysfunction in murine lupus and the mechanism of lessened photosensitivity with improved lymphatic drainage. If similar immune circuitry defects are present in patients with SLE, altering lymphatics could be a novel target for new therapeutics.
Acknowledgments Lupus Research Alliance
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