IL-7 Deficiency Exacerbates Atopic Dermatitis in NC/Nga Mice

Interleukin-7 (IL-7) plays a vital role in the homeostasis of CD4(+) and CD8(+) T cells. Although IL-7 has been implicated in T helper (Th)1- and Th17-mediated autoinflammatory diseases, its role in Th2-type allergic disorders, such as atopic dermatitis (AD), remains unclear. Thus, to elucidate the effects of IL-7 deficiency on AD development, we generated IL-7-deficient AD-prone mice by backcrossing IL-7 knockout (KO) B6 mice onto the NC/Nga (NC) mouse strain, a model for human AD. As expected, IL-7 KO NC mice displayed defective development of conventional CD4(+) and CD8(+) T cells compared with wild type (WT) NC mice. However, IL-7 KO NC mice presented with enhanced AD clinical scores, IgE hyperproduction, and increased epidermal thickness compared with WT NC mice. Moreover, IL-7 deficiency decreased Th1, Th17, and IFN-?-producing CD8(+) T cells but increased Th2 cells in the spleen of NC mice, indicating that a reduced Th1/Th2 ratio correlates with severity of AD pathogenesis. Furthermore, significantly more basophils and mast cells infiltrated the skin lesions of IL-7 KO NC mice. Taken together, our findings suggest that IL-7 could be a useful therapeutic target for treating Th2-mediated skin inflammations, such as AD.

Automated summary

Interleukin-7 (IL-7) is important in maintaining the balance of CD4(+) and CD8(+) T cells. However, its role in allergic disorders, such as atopic dermatitis (AD), has not been well understood. By studying IL-7-deficient AD-prone mice, it was found that IL-7 deficiency worsened AD development, indicating that IL-7 could be a potential therapeutic target for treating AD.