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Biomedicines
Volume 9
Issue 11
10.3390/biomedicines9111619
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Article

Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14Tg NC/Nga Mice

by
Hyun Jung Park
1,†,
Tae-Cheol Kim
1,†,
Yun Hoo Park
1,†,
Sung Won Lee
1,
Jungmin Jeon
1,
Se-Ho Park
2,
Luc Van Kaer
3 and
Seokmann Hong
1,*
1
Department of Integrative Bioscience and Biotechnology, Institute of Anticancsoer Medicine Development, Sejong University, Seoul 05006, Korea
2
Department of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
3
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2021, 9(11), 1619; https://doi.org/10.3390/biomedicines9111619
Submission received: 26 August 2021 / Revised: 12 October 2021 / Accepted: 29 October 2021 / Published: 4 November 2021
(This article belongs to the Special Issue Immune-Mediated Skin Diseases: From Pathophysiology to Novel Therapeutic Approaches)
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Abstract

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.
Keywords: atopic dermatitis; NC/Nga mice; iNKT cells; Vα14 TCR transgenic mice; α-GalCer atopic dermatitis; NC/Nga mice; iNKT cells; Vα14 TCR transgenic mice; α-GalCer

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MDPI and ACS Style

Park, H.J.; Kim, T.-C.; Park, Y.H.; Lee, S.W.; Jeon, J.; Park, S.-H.; Van Kaer, L.; Hong, S. Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14Tg NC/Nga Mice. Biomedicines 2021, 9, 1619. https://doi.org/10.3390/biomedicines9111619

AMA Style

Park HJ, Kim T-C, Park YH, Lee SW, Jeon J, Park S-H, Van Kaer L, Hong S. Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14Tg NC/Nga Mice. Biomedicines. 2021; 9(11):1619. https://doi.org/10.3390/biomedicines9111619

Chicago/Turabian Style

Park, Hyun Jung, Tae-Cheol Kim, Yun Hoo Park, Sung Won Lee, Jungmin Jeon, Se-Ho Park, Luc Van Kaer, and Seokmann Hong. 2021. "Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14Tg NC/Nga Mice" Biomedicines 9, no. 11: 1619. https://doi.org/10.3390/biomedicines9111619

APA Style

Park, H. J., Kim, T.-C., Park, Y. H., Lee, S. W., Jeon, J., Park, S.-H., Van Kaer, L., & Hong, S. (2021). Repeated α-GalCer Administration Induces a Type 2 Cytokine-Biased iNKT Cell Response and Exacerbates Atopic Skin Inflammation in Vα14Tg NC/Nga Mice. Biomedicines, 9(11), 1619. https://doi.org/10.3390/biomedicines9111619

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