Neutrophil Cathepsin G Regulates Dendritic Cell Production of IL-12 During Development of CD4 T Cell Responses to Antigens in the Skin
| Autor: | Nina Dvorina, Danielle D. Kish, Stephen A. Stohlman, William M. Baldwin, Robert L. Fairchild, Susie Min |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cathepsin G Neutrophils Immunology Dermatitis Contact Article Receptors Interleukin-8B 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Antigen medicine Immunology and Allergy Cytotoxic T cell Animals Sensitization Skin Mice Knockout Mice Inbred BALB C integumentary system Effector Dendritic cell Dendritic Cells Molecular biology Interleukin-12 Mice Inbred C57BL medicine.anatomical_structure chemistry Interleukin 12 Female Haptens CD8 030215 immunology |
| Popis: | Contact hypersensitivity (CHS) is a CD8 T cell–mediated response to hapten skin sensitization and challenge. Sensitization of wild-type (WT) mice induces hapten-reactive effector CD8 T cells producing IFN-γ and IL-17– and IL-4–producing CD4 T cells that cannot mediate CHS. Although CXCR2-dependent Ly6G+ (neutrophil) cell recruitment into hapten-challenged skin is required to direct effector CD8 T cell infiltration into the challenge site to elicit CHS, 2,4-dinitrofluorobenezene (DNFB) sensitization of CXCR2−/− mice and neutrophil-depleted WT mice induced both hapten-reactive CD4 and CD8 T cells producing IFN-γ and IL-17. CD4 T cell–mediated CHS responses were not generated during DNFB sensitization of neutrophil-depleted WT mice treated with anti–IL-12 mAb or neutrophil-depleted IL-12−/− mice. Neutrophil depletion during DNFB sensitization of WT mice markedly increased IL-12–producing hapten-primed dendritic cell numbers in the skin-draining lymph nodes. Sensitization of mice lacking the neutrophil serine protease cathepsin G (CG)–induced hapten-reactive CD4 and CD8 T cells producing IFN-γ and IL-17 with elevated and elongated CHS responses to DNFB challenge. Induction of CHS effector CD4 T cells producing IFN-γ in neutrophil-depleted WT mice was eliminated by s.c. injection of active, but not inactivated, CG during sensitization. Thus, hapten skin sensitization induces neutrophil release of CG that systemically inhibits hapten-presenting dendritic cell production of IL-12 and the development of hapten-reactive CD4 T cells to IFN-γ–producing CHS effector cells. |
| Databáze: | OpenAIRE |
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