Lymphatic function regulates contact hypersensitivity dermatitis in obesity Journal Article

Authors: Savetsky, I. L.; Albano, N. J.; Cuzzone, D. A.; Gardenier, J. C.; Torrisi, J. S.; Nores, G. D. G.; Nitti, M. D.; Hespe, G. E.; Nelson, T. S.; Kataru, R. P.; Dixon, J. B.; Mehrara, B. J.
Article 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. © 2015 The Society for Investigative Dermatology.
Keywords: controlled study; protein expression; nonhuman; t lymphocyte; animal cell; mouse; animal tissue; interleukin 4; obesity; immunoregulation; vasculotropin c; endothelium cell; lymph vessel endothelium; lymphangiogenesis; lymphatic system; immune response; gamma interferon; cytokine production; dermatitis; antibody production; nitric oxide synthase; lymphatic system disease; secondary lymphoid tissue chemokine; contact allergy; recombinant vasculotropin; male; priority journal; article; diet induced obesity; skin stimulation
Journal Title: Journal of Investigative Dermatology
Volume: 135
Issue: 11
ISSN: 0022-202X
Publisher: Nature Publishing Group  
Date Published: 2015-11-01
Start Page: 2742
End Page: 2752
Language: English
DOI: 10.1038/jid.2015.283
PROVIDER: scopus
PMCID: PMC4641050
PUBMED: 26176761
Notes: Export Date: 2 December 2015 -- Source: Scopus
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MSK Authors
  1. Babak Mehrara
    249 Mehrara
  2. Nicholas James Albano
    19 Albano
  3. Daniel Adam Cuzzone
    23 Cuzzone
  4. Jeremy   Torrisi
    25 Torrisi
  5. Geoffrey Eckerson Hespe
    20 Hespe
  6. Raghu Prasad Kataru
    20 Kataru
  7. Matthew   Nitti
    12 Nitti