Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14Tg NC/Nga Mice
| Autor: | Jungmin Jeon, Sung Won Lee, Yun Hoo Park, Luc Van Kaer, Tae-Cheol Kim, Hyun Jung Park, Seokmann Hong, Se Ho Park |
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| Rok vydání: | 2021 |
| Předmět: |
NC/Nga mice
QH301-705.5 medicine.medical_treatment Medicine (miscellaneous) chemical and pharmacologic phenomena Inflammation Immunoglobulin E Article General Biochemistry Genetics and Molecular Biology Pathogenesis Immune system medicine Biology (General) iNKT cells Interleukin 4 atopic dermatitis biology business.industry T-cell receptor FOXP3 Vα14 TCR transgenic mice α-GalCer Cytokine Immunology biology.protein medicine.symptom business |
| Zdroj: | Biomedicines Biomedicines, Vol 9, Iss 1619, p 1619 (2021) Volume 9 Issue 11 |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines9111619 |
| Popis: | We have previously shown that Vα14 TCR Tg (Vα14Tg) NC/Nga (NC) mice contain increased numbers of double-negative (DN) invariant natural killer T (iNKT) cells that protect against spontaneous development of atopic dermatitis (AD). iNKT cells can regulate immune responses by producing various cytokines such as IFNγ and IL4 rapidly upon stimulation with α-galactosylceramide (α-GalCer), a prototypical iNKT cell agonist. However, the precise role of α-GalCer-activated iNKT cells in AD development remains unclear. Therefore, we examined whether repeated activation of iNKT cells with α-GalCer can regulate the pathogenesis of AD in Vα14Tg NC mice. We found that Vα14Tg NC mice injected repeatedly with α-GalCer display exacerbated AD symptoms (e.g., a higher clinical score, IgE hyperproduction, and increased numbers of splenic mast cells and neutrophils) compared with vehicle-injected Vα14Tg NC mice. Moreover, the severity of AD pathogenesis in α-GalCer-injected Vα14Tg NC mice correlated with increased Th2 cells but reduced Th1 and Foxp3+ Treg cells. Furthermore, the resulting alterations in the Th1/Th2 and Treg/Th2 balance were strongly associated with a biased expansion of type 2 cytokine-deviated iNKT cells in α-GalCer-treated Vα14Tg NC mice. Collectively, our results have demonstrated the adverse effect of repeated α-GalCer treatment on skin inflammation mediated by type 2 immunity. |
| Databáze: | OpenAIRE |
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