Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice

We have previously shown that Vα14 TCR Tg (Vα14<sup>Tg</sup>) 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 pro...

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Autores principales:	Hyun Jung Park, Tae-Cheol Kim, Yun Hoo Park, Sung Won Lee, Jungmin Jeon, Se-Ho Park, Luc Van Kaer, Seokmann Hong
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/56541c812d8f4570b5a00402c028bfab
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spelling	oai:doaj.org-article:56541c812d8f4570b5a00402c028bfab2021-11-25T16:49:40ZRepeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice10.3390/biomedicines91116192227-9059https://doaj.org/article/56541c812d8f4570b5a00402c028bfab2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1619https://doaj.org/toc/2227-9059We have previously shown that Vα14 TCR Tg (Vα14<sup>Tg</sup>) 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 Vα14<sup>Tg</sup> NC mice. We found that Vα14<sup>Tg</sup> 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 Vα14<sup>Tg</sup> NC mice. Moreover, the severity of AD pathogenesis in α-GalCer-injected Vα14<sup>Tg</sup> NC mice correlated with increased Th2 cells but reduced Th1 and Foxp3<sup>+</sup> 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 Vα14<sup>Tg</sup> NC mice. Collectively, our results have demonstrated the adverse effect of repeated α-GalCer treatment on skin inflammation mediated by type 2 immunity.Hyun Jung ParkTae-Cheol KimYun Hoo ParkSung Won LeeJungmin JeonSe-Ho ParkLuc Van KaerSeokmann HongMDPI AGarticleatopic dermatitisNC/Nga miceiNKT cellsVα14 TCR transgenic miceα-GalCerBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1619, p 1619 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) QH301-705.5
spellingShingle	atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) QH301-705.5 Hyun Jung Park Tae-Cheol Kim Yun Hoo Park Sung Won Lee Jungmin Jeon Se-Ho Park Luc Van Kaer Seokmann Hong Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice
description	We have previously shown that Vα14 TCR Tg (Vα14<sup>Tg</sup>) 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 Vα14<sup>Tg</sup> NC mice. We found that Vα14<sup>Tg</sup> 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 Vα14<sup>Tg</sup> NC mice. Moreover, the severity of AD pathogenesis in α-GalCer-injected Vα14<sup>Tg</sup> NC mice correlated with increased Th2 cells but reduced Th1 and Foxp3<sup>+</sup> 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 Vα14<sup>Tg</sup> NC mice. Collectively, our results have demonstrated the adverse effect of repeated α-GalCer treatment on skin inflammation mediated by type 2 immunity.
format	article
author	Hyun Jung Park Tae-Cheol Kim Yun Hoo Park Sung Won Lee Jungmin Jeon Se-Ho Park Luc Van Kaer Seokmann Hong
author_facet	Hyun Jung Park Tae-Cheol Kim Yun Hoo Park Sung Won Lee Jungmin Jeon Se-Ho Park Luc Van Kaer Seokmann Hong
author_sort	Hyun Jung Park
title	Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice
title_short	Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice
title_full	Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice
title_fullStr	Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice
title_full_unstemmed	Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice
title_sort	repeated α-galcer administration induces a type 2 cytokine-biased inkt cell response and exacerbates atopic skin inflammation in vα14<sup>tg</sup> nc/nga mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/56541c812d8f4570b5a00402c028bfab
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Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14<sup>Tg</sup> NC/Nga Mice

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