Selective Expansion of Double-Negative iNKT Cells Inhibits the Development of Atopic Dermatitis in Vα14 TCR Transgenic NC/Nga Mice by Increasing Memory-Type CD8+ T and Regulatory CD4+ T Cells.

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.