Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity

Mol Immunol. 2023 Aug:160:133-149. doi: 10.1016/j.molimm.2023.07.002. Epub 2023 Jul 8.

Abstract

Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4+ T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-β-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4+ cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-κB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases.

Keywords: Atopic dermatitis; IL-2; Jing-Fang powder ethyl acetate extracts; NF-κB/MAPK pathways; T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Dermatitis, Atopic* / chemically induced
  • Dermatitis, Atopic* / drug therapy
  • Interleukin-2
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Plant Extracts / pharmacology
  • Powders / adverse effects
  • Powders / metabolism

Substances

  • Interleukin-2
  • ethyl acetate
  • Powders
  • NF-kappa B
  • Cytokines
  • Plant Extracts