Spontaneous development of atopic dermatitis (AD) in NC/Nga (NC) mice has been attributed to a deficiency in invariant NK T (iNKT) cells. To elucidate the precise role of iNKT cells in AD development of NC mice, we employed two distinct murine models of iNKT cell over-representation: Vβ8 TCR congenic and Vα14 TCR transgenic NC mice. We found that Vα14 TCR transgenic (Vα14Tg) but not Vβ8 TCR congenic (Vβ8Cg) NC mice exhibited reduced AD development, which was attributed to both quantitative and qualitative changes in iNKT cells such as a biased expansion of the double-negative iNKT subset. Adoptive transfer experiments confirmed that iNKT cells from Vα14Tg mice but not from Vβ8Cg mice were responsible for protecting NC mice from AD development. Double-negative iNKT cells from Vα14Tg NC mice showed a T helper type-1‒dominant cytokine profile, which may account for the expansion of CD4+ regulatory T cells and memory-type CD8+ T cells. Furthermore, the adoptive transfer of CD8+ T cells from Vα14Tg NC mice into AD-susceptible wild-type NC mice suppressed AD in recipient NC mice. Taken together, our results have identified double-negative iNKT cells as promising cellular targets to prevent AD pathogenesis.
Bibliographical noteFunding Information:
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-2016R1D1A1A09919293 and NRF-2019R1A2C1009926 to SH, NRF-2018R1D1A1B07049495 to HJP, and NRF-2018R1D1A1A02086057 to SWL)
© 2021 The Authors
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology