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.
Bibliographical noteFunding Information:
Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1I1A1A01051465 to H.J.P.; NRF-2021R1I1A1A01054418 to S.W.L.; NRF-2019R1A2C1009926 to S.H.).
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Atopic dermatitis
- INKT cells
- NC/Nga mice
- Vα14 TCR transgenic mice
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)