Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 5, Pages 1827-1834Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700739
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Funding
- National Institutes of Health [K08 AR06379, K08 HL105537]
- Duke Physician-Scientist Strong Start Award
- Dermatology Foundation Research grant
- National Natural Science Foundation [81201243]
- China Postdoctoral Science Foundation [2014M562671]
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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/M Phi), which renders those cells ineffectual in suppressing skin inflammation. Mice lacking Arg1 in M Phi develop increased CHS characterized by elevated ear thickening, mono/M Phi 2 dominated dermal inflammation, and increased iNOS and IL-6 expression compared with control mice. Treatment of Arg1(flox/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/M Phi in suppressing CHS through dampening Nos2 expression. These results support that increasing Arg1 may be a potential therapeutic avenue in treating allergic contact dermatitis.
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