Arginase1 Deficiency in Monocytes/Macrophages Upregulates Inducible Nitric Oxide Synthase To Promote Cutaneous Contact Hypersensitivity.
Jutamas SuwanpradidMichael C ShihLauren PontiusBin YangAnastasiya BirukovaEmma Guttman-YasskyDavid L CorcoranLoretta G QueRobert M TigheAmanda S MacLeodPublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
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.
Keyphrases
- nitric oxide synthase
- nitric oxide
- mouse model
- high fat diet induced
- poor prognosis
- end stage renal disease
- oxidative stress
- innate immune
- induced apoptosis
- signaling pathway
- ejection fraction
- chronic kidney disease
- newly diagnosed
- dendritic cells
- drug induced
- peripheral blood
- wild type
- peritoneal dialysis
- type diabetes
- binding protein
- prognostic factors
- replacement therapy
- immune response
- cell cycle arrest
- skeletal muscle
- allergic rhinitis
- soft tissue