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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Autor*in:	Hyun Jung Park [verfasserIn] Tae-Cheol Kim [verfasserIn] Yun Hoo Park [verfasserIn] Sung Won Lee [verfasserIn] Jungmin Jeon [verfasserIn] Se-Ho Park [verfasserIn] Luc Van Kaer [verfasserIn] Seokmann Hong [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer

Übergeordnetes Werk:	In: Biomedicines - MDPI AG, 2014, 9(2021), 11, p 1619
Übergeordnetes Werk:	volume:9 ; year:2021 ; number:11, p 1619

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/biomedicines9111619

Katalog-ID:	DOAJ071573232

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520			\|a 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.
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allfields	10.3390/biomedicines9111619 doi (DE-627)DOAJ071573232 (DE-599)DOAJ56541c812d8f4570b5a00402c028bfab DE-627 ger DE-627 rakwb eng QH301-705.5 Hyun Jung Park verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) Tae-Cheol Kim verfasserin aut Yun Hoo Park verfasserin aut Sung Won Lee verfasserin aut Jungmin Jeon verfasserin aut Se-Ho Park verfasserin aut Luc Van Kaer verfasserin aut Seokmann Hong verfasserin aut In Biomedicines MDPI AG, 2014 9(2021), 11, p 1619 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:9 year:2021 number:11, p 1619 https://doi.org/10.3390/biomedicines9111619 kostenfrei https://doaj.org/article/56541c812d8f4570b5a00402c028bfab kostenfrei https://www.mdpi.com/2227-9059/9/11/1619 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 11, p 1619
spelling	10.3390/biomedicines9111619 doi (DE-627)DOAJ071573232 (DE-599)DOAJ56541c812d8f4570b5a00402c028bfab DE-627 ger DE-627 rakwb eng QH301-705.5 Hyun Jung Park verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) Tae-Cheol Kim verfasserin aut Yun Hoo Park verfasserin aut Sung Won Lee verfasserin aut Jungmin Jeon verfasserin aut Se-Ho Park verfasserin aut Luc Van Kaer verfasserin aut Seokmann Hong verfasserin aut In Biomedicines MDPI AG, 2014 9(2021), 11, p 1619 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:9 year:2021 number:11, p 1619 https://doi.org/10.3390/biomedicines9111619 kostenfrei https://doaj.org/article/56541c812d8f4570b5a00402c028bfab kostenfrei https://www.mdpi.com/2227-9059/9/11/1619 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 11, p 1619
allfields_unstemmed	10.3390/biomedicines9111619 doi (DE-627)DOAJ071573232 (DE-599)DOAJ56541c812d8f4570b5a00402c028bfab DE-627 ger DE-627 rakwb eng QH301-705.5 Hyun Jung Park verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) Tae-Cheol Kim verfasserin aut Yun Hoo Park verfasserin aut Sung Won Lee verfasserin aut Jungmin Jeon verfasserin aut Se-Ho Park verfasserin aut Luc Van Kaer verfasserin aut Seokmann Hong verfasserin aut In Biomedicines MDPI AG, 2014 9(2021), 11, p 1619 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:9 year:2021 number:11, p 1619 https://doi.org/10.3390/biomedicines9111619 kostenfrei https://doaj.org/article/56541c812d8f4570b5a00402c028bfab kostenfrei https://www.mdpi.com/2227-9059/9/11/1619 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 11, p 1619
allfieldsGer	10.3390/biomedicines9111619 doi (DE-627)DOAJ071573232 (DE-599)DOAJ56541c812d8f4570b5a00402c028bfab DE-627 ger DE-627 rakwb eng QH301-705.5 Hyun Jung Park verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) Tae-Cheol Kim verfasserin aut Yun Hoo Park verfasserin aut Sung Won Lee verfasserin aut Jungmin Jeon verfasserin aut Se-Ho Park verfasserin aut Luc Van Kaer verfasserin aut Seokmann Hong verfasserin aut In Biomedicines MDPI AG, 2014 9(2021), 11, p 1619 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:9 year:2021 number:11, p 1619 https://doi.org/10.3390/biomedicines9111619 kostenfrei https://doaj.org/article/56541c812d8f4570b5a00402c028bfab kostenfrei https://www.mdpi.com/2227-9059/9/11/1619 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 11, p 1619
allfieldsSound	10.3390/biomedicines9111619 doi (DE-627)DOAJ071573232 (DE-599)DOAJ56541c812d8f4570b5a00402c028bfab DE-627 ger DE-627 rakwb eng QH301-705.5 Hyun Jung Park verfasserin aut 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 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer Biology (General) Tae-Cheol Kim verfasserin aut Yun Hoo Park verfasserin aut Sung Won Lee verfasserin aut Jungmin Jeon verfasserin aut Se-Ho Park verfasserin aut Luc Van Kaer verfasserin aut Seokmann Hong verfasserin aut In Biomedicines MDPI AG, 2014 9(2021), 11, p 1619 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:9 year:2021 number:11, p 1619 https://doi.org/10.3390/biomedicines9111619 kostenfrei https://doaj.org/article/56541c812d8f4570b5a00402c028bfab kostenfrei https://www.mdpi.com/2227-9059/9/11/1619 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 11, p 1619
language	English
source	In Biomedicines 9(2021), 11, p 1619 volume:9 year:2021 number:11, p 1619
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authorswithroles_txt_mv	Hyun Jung Park @@aut@@ Tae-Cheol Kim @@aut@@ Yun Hoo Park @@aut@@ Sung Won Lee @@aut@@ Jungmin Jeon @@aut@@ Se-Ho Park @@aut@@ Luc Van Kaer @@aut@@ Seokmann Hong @@aut@@
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author	Hyun Jung Park
spellingShingle	Hyun Jung Park misc QH301-705.5 misc atopic dermatitis misc NC/Nga mice misc iNKT cells misc Vα14 TCR transgenic mice misc α-GalCer misc Biology (General) 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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topic_title	QH301-705.5 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 atopic dermatitis NC/Nga mice iNKT cells Vα14 TCR transgenic mice α-GalCer
topic	misc QH301-705.5 misc atopic dermatitis misc NC/Nga mice misc iNKT cells misc Vα14 TCR transgenic mice misc α-GalCer misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc atopic dermatitis misc NC/Nga mice misc iNKT cells misc Vα14 TCR transgenic mice misc α-GalCer misc Biology (General)
topic_browse	misc QH301-705.5 misc atopic dermatitis misc NC/Nga mice misc iNKT cells misc Vα14 TCR transgenic mice misc α-GalCer misc Biology (General)
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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
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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
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author_browse	Hyun Jung Park Tae-Cheol Kim Yun Hoo Park Sung Won Lee Jungmin Jeon Se-Ho Park Luc Van Kaer Seokmann Hong
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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
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title_auth	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
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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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
url	https://doi.org/10.3390/biomedicines9111619 https://doaj.org/article/56541c812d8f4570b5a00402c028bfab https://www.mdpi.com/2227-9059/9/11/1619 https://doaj.org/toc/2227-9059
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author2	Tae-Cheol Kim Yun Hoo Park Sung Won Lee Jungmin Jeon Se-Ho Park Luc Van Kaer Seokmann Hong
author2Str	Tae-Cheol Kim Yun Hoo Park Sung Won Lee Jungmin Jeon Se-Ho Park Luc Van Kaer Seokmann Hong
ppnlink	750370483
callnumber-subject	QH - Natural History and Biology
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doi_str	10.3390/biomedicines9111619
callnumber-a	QH301-705.5
up_date	2024-07-03T21:00:41.450Z
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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. 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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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