An inhibitory immunoreceptor, Allergin-1, suppresses FITC-induced type 2 contact hypersensitivity

• Published in: Biochemical and biophysical research communications 2021-11, Vol.579, p.146-152
• Main Authors: Almeida, Mariana Silva, Shibagaki, Shohei, Tahara-Hanaoka, Satoko, Shibayama, Shiro, Shibuya, Akira
• Format: Article
• Language: English
• Subjects: Allergic contact dermatitis; Allergin-1; Animals; CD4-Positive T-Lymphocytes - cytology; Contact hypersensitivity; Dendritic Cells - cytology; Dendritic Cells - metabolism; Dermal dendritic cell; Dermatitis, Contact - metabolism; Dinitrofluorobenzene - chemistry; Female; Fluorescein-5-isothiocyanate - chemistry; Hypersensitivity, Immediate; Interleukin-10 - biosynthesis; Interleukin-13 - biosynthesis; Interleukin-5 - biosynthesis; Mice; Mice, Inbred BALB C; Receptors, Immunologic - metabolism; Receptors, Immunologic - physiology; Skin - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.09.048

Although allergic contact dermatitis (ACD) is the most common T cell-mediated inflammatory responses against an allergen in the skin, the pathogenesis of ACD remains incompletely understood. In the sensitization phase in ACD, hapten-bearing dermal dendritic cells (DCs) play a pivotal role in the transport of an antigen to the lymph nodes (LNs), where they present the antigen to naïve T cells. Here we report that Allergin-1, an inhibitory immunoreceptor containing immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic region, is highly expressed on dermal DCs. Mice deficient in Allergin-1 exhibited exacerbated fluorescein isothiocyanate (FITC)-induced type 2 contact hypersensitivity (CHS) such as ear swelling and skin eosinophilia. Allergin-1-deficient mice also showed larger numbers of CD4+ T cells and FITC-bearing DCs and greater expressions of type 2 cytokines, including IL-5, IL-10 and IL-13, in the draining LNs than did wild type mice. In sharp contrast, Allergin-1-deficient mice showed comparable level of type 1 CHS induced by 2,4-dinitrofluorobenzene (DNFB). These results suggest that Allergin-1 on dermal DC inhibits type 2, but not type 1, immune responses in the sensitization phase of CHS. •Allergin-1 is highly expressed on dermal dendritic cells.•Allergin-1 inhibits type 2, but not type 1 contact hypersensitivity.•Allergin-1 suppresses dermal DC activation during the sensitization phase.