Arginase1 Deficiency in Monocytes/Macrophages Upregulates Inducible Nitric Oxide Synthase To Promote Cutaneous Contact Hypersensitivity.

Journal Issue (Journal Article)

The innate immune components that modulate allergic contact hypersensitivity (CHS) responses are poorly defined. Using human skin from contact dermatitis patients and a mouse model of CHS, we find that hapten allergens disrupt the Arginase1 (Arg1) and inducible NO synthase (iNOS) dynamic in monocytes/macrophages (mono/MΦ), which renders those cells ineffectual in suppressing skin inflammation. Mice lacking Arg1 in MΦ develop increased CHS characterized by elevated ear thickening, mono/MΦ-dominated dermal inflammation, and increased iNOS and IL-6 expression compared with control mice. Treatment of Arg1flox/flox; LysMCre+/- mice with a selective NOS inhibitor or knockout of Nos2, encoding iNOS, significantly ameliorates CHS. Our findings suggest a critical role for Arg1 in mono/MΦ in suppressing CHS through dampening Nos2 expression. These results support that increasing Arg1 may be a potential therapeutic avenue in treating allergic contact dermatitis.

Full Text

Duke Authors

Cited Authors

  • Suwanpradid, J; Shih, M; Pontius, L; Yang, B; Birukova, A; Guttman-Yassky, E; Corcoran, DL; Que, LG; Tighe, RM; MacLeod, AS

Published Date

  • September 1, 2017

Published In

Volume / Issue

  • 199 / 5

Start / End Page

  • 1827 - 1834

PubMed ID

  • 28747341

Pubmed Central ID

  • PMC5568483

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1700739


  • eng

Conference Location

  • United States