title: Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.
abstract: 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.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Ira L
authors.initials: IL
authors.lastname: Savetsky
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Albano
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Cuzzone
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Gardenier
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Torrisi
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Gabriela D
authors.initials: GD
authors.lastname: García Nores
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Nitti
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Hespe
authors.affiliation: Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Nelson
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Raghu P
authors.initials: RP
authors.lastname: Kataru
authors.affiliation: Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: J Brandon
authors.initials: JB
authors.lastname: Dixon
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address: mehrarab@mskcc.org.
authors.forename: Babak J
authors.initials: BJ
authors.lastname: Mehrara
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008208:Lymphatic System / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D011897:Random Allocation; D012016:Reference Values; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A