Arginase1 deficiency in monocytes/macrophages up-regulates iNOS to promote cutaneous contact hypersensitivity

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 nitric oxide synthase (iNOS or Nos2) dynamic in monocytes/macrophages, which renders those cells ineffectual in suppressing skin inflammation. Mice lacking Arg1 in macrophages develop increased CHS characterized by elevated ear thickening, monocytes/macrophage-dominated dermal inflammation, and increased iNOS and IL-6 expression compared to control mice. Treatment of Arg1 flox/flox ; LysMCre +/− mice with a selective NOS inhibitor or knockout of iNOS significantly ameliorated CHS. Our findings suggest a critical role for Arg1 in monocytes/macrophages in suppressing CHS through dampening Nos2 expression. These results may support that increasing Arg1 may be a potential therapeutic avenue in treating allergic contact dermatitis.