Licoricidin Abrogates T Cell Activation by Modulating PTPN1 Activity and Attenuates Atopic Dermatitis In Vivo.

Licoricidin, the fifth-highest fraction among the isolated 48 molecules from Glycyrrhiza uralensis extracts, has been known as anti-inflammatory bioactive molecules, however, few studies have shown its inhibitory effect on T cell activation and atopic dermatitis. The present study examined the therapeutic potential of licoricidin in atopic dermatitis by modulating T cell activation with molecular mechanism. Licoricidin attenuated the expression of IL-2 mRNA in stimulated T cells without cytotoxicity. Since tyrosine-protein phosphatase non-receptor type 1 (PTPN1) was predicted to interact physically with licoricidin in T cells in silico analysis, the results of PTPN1 activity assay and phosphorylation study predicted that licoricidin might abrogate the activity of PTPN1 during T cell activation. Pre-treatment with licoricidin controlled the dephosphorylation of Lck on T cell receptor (TCR)-mediated stimulation. Moreover, licoricidin alleviated the symptoms of DNCB/mite extract-induced AD, including ear thickness and serum IgE level. Microscopic analysis also showed the effects of licoricidin on the thickness of dermis/epidermis and infiltration of immune cells. Furthermore, mRNA level of pro-inflammatory cytokines were attenuated in the ear lesions of licoricidin-treated AD mice. Therefore, licoricidin has therapeutic potential for treating AD and its underlying mechanism involves effective modulation of T cell activation by controlling PTPN1 to maintain Lck phosphorylation.