Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.
Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.
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DOI：
10.1038/jid.2015.283
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Mehrara BJ
中科院分区：
文献类型：
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作者：
Savetsky IL;Albano NJ;Cuzzone DA;Gardenier JC;Torrisi JS;García Nores GD;Nitti MD;Hespe GE;Nelson TS;Kataru RP;Dixon JB;Mehrara BJ
Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C–C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response.
