Lack of Type 2 Innate Lymphoid Cells Promotes a Type I-Driven Enhanced Immune Response in Contact Hypersensitivity
| Autor: | David Rafei-Shamsabadi, Karolina Ebert, Yakup Tanriver, Stefan F. Martin, Sebastian J. Arnold, Saskia van de Poel, Christoph S.N. Klose, Britta Dorn, Andreas Diefenbach, Timotheus Y.F. Halim, Thilo Jakob, Andrew N. J. McKenzie, Stefanie Kunz |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Adoptive cell transfer T-Lymphocytes medicine.medical_treatment Dermatology TNCB 2 4 6-Trinitrochlorobenzene Biochemistry Article Mice 03 medical and health sciences Immune system RAR-related orphan receptor gamma medicine Animals MHC major histocompatibility complex Th T helper Molecular Biology Allergic contact dermatitis Skin TNF tumor necrosis factor Innate immune system Chemistry Innate lymphoid cell ILC innate lymphoid cell Cell Biology medicine.disease Adoptive Transfer CHS contact hypersensitivity Immunity Innate Disease Models Animal 030104 developmental biology Cytokine Dermatitis Allergic Contact Immunology LN lymph node Female NK natural killer Hapten |
| Zdroj: | The Journal of Investigative Dermatology |
| ISSN: | 0022-202X |
| Popis: | Allergic contact dermatitis and its animal model, contact hypersensitivity, are T-cell-mediated inflammatory skin diseases that require activation of the innate immune system. Here we investigate the role of innate lymphoid cells (ILCs) during the elicitation phase of 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity using EomesGfp/+ x Rorc(γt)-CreTg x Rosa26RYfp/+ reporter mice. Ear swelling responses, cutaneous ILC numbers, and cytokine production were determined at different time points. Functional analyses were performed in a CD90.1/.2 congenic adoptive transfer model that allowed selective antibody-mediated depletion of ILCs before hapten challenge, and in Rorasg/floxIl7rCre/+ mice, which lack ILC2. Hapten challenge induced early increases of natural killer cells in skin and ear draining lymph nodes corresponding to the peak ear swelling response. In contrast, ILC1, 2, and 3 showed a delayed increase in numbers corresponding to the contact hypersensitivity resolution phase. Hapten challenge induced increased marker cytokines in all ILC subtypes and an activated phenotype in ILC2. Depletion of all ILC resulted in a significantly enhanced ear swelling response. Similarly, ILC2-deficient mice (Rorasg/floxIl7rCre/+) displayed increased ear swelling responses on hapten challenge, suggesting that ILC2 act as negative regulators in the type 1-dominated immune response of contact hypersensitivity. |
| Databáze: | OpenAIRE |
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