3,3'-Diindolylmethane alleviates acute atopic dermatitis by regulating T cell differentiation in a mouse model

Mol Immunol. 2021 Feb;130:104-112. doi: 10.1016/j.molimm.2020.11.013. Epub 2020 Dec 11.

Abstract

Atopic dermatitis is a severe, chronic relapsing inflammatory disease of the skin with family clustering. It is characterized into acute phase, which is dominated by T helper 2-type immune responses, and chronic phase, which is dominated by T helper 1-type immune responses. Studies have shown that 3,3'-diindolylmethane not only has antitumor effects but also can relieve symptoms of inflammatory diseases by inhibiting the nuclear factor-κB signaling pathway and regulating T cell differentiation. To study the effect of 3,3'-diindolylmethane on atopic dermatitis and the underlying mechanism, a mouse model of acute atopic dermatitis was established using 2,4-dinitrofluorobenzene. After intraperitoneal injection of 3,3'-diindolylmethane, skin erythema and edema in mice were significantly alleviated. Furthermore, 3,3'-diindolylmethane reduced immune activation, probably by inhibiting the secretion of thymic stromal lymphopoietin by keratinocytes. 3,3'-Diindolylmethane also promoted the differentiation of regulatory T cells and inhibited the activation of T helper 2 and T helper 17 cells to reduce atopic dermatitis-related immune responses. However, it showed no significant effect on the differentiation of T helper 1 cells. These results indicate that 3,3'-diindolylmethane has a significant inhibitory effect on T helper 2 cells in the acute phase of atopic dermatitis. Our findings may provide not only more insights into the pathological mechanism of AD, but also a new candidate medicine for it.

Keywords: 3,3'-Diindolylmethane; Atopic dermatitis; Regulatory T cell; T-helper cell; Thymic stromal lymphopoietin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Disease Models, Animal
  • Female
  • HaCaT Cells
  • Humans
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Keratinocytes / drug effects
  • Keratinocytes / physiology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Skin / drug effects
  • Skin / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / physiology

Substances

  • Indoles
  • 3,3'-diindolylmethane