N-acetyl-L-alanine ameliorates atopic dermatitis-like symptoms by suppressing Th2 differentiation in DNFB-induced NC/Nga mice.

Atopic dermatitis (AD) is a chronic dermatological disorder characterized by intense pruritus and eczematous lesions. Repeated topical application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice produces AD-like clinical symptoms that closely resemble human AD. N-Acetyl-L-Alanine (L-NAA), a derivative of L-Alanine, has unknown biological and physiological effects on cutaneous tissue. In this study, we investigated whether L-NAA modifies AD-like symptoms elicited by ongoing DNFB exposure in NC/Nga mice. Topical administration of L-NAA markedly attenuated the development of AD-like cutaneous lesions triggered by DNFB. L-NAA treatment further suppressed DNFB-induced infiltration of eosinophils and mast cells and prevented the increase of serum IgE resulting from DNFB application. L-NAA treatment decreased DNFB-stimulated expression of IL-4, a Th2-associated cytokine, but increased IFN-γ expression, indicative of Th1 activity, within the skin lesions. In addition, L-NAA prevented the DNFB-driven upregulation of GATA3, a central regulator of Th2 lineage differentiation, in CD4＋ cells, with no effect on T-bet, the principal regulator of Th1 cells. These findings indicate that L-NAA can limit Th2 differentiation in the AD mouse model. Therefore, L-NAA may serve as a promising therapeutic and immunomodulatory compound against AD.