Baicalin modulates the Treg/Teff balance to alleviate uveitis by activating the aryl hydrocarbon receptor

Biochem Pharmacol. 2018 Aug:154:18-27. doi: 10.1016/j.bcp.2018.04.006. Epub 2018 Apr 13.

Abstract

Autoimmune uveitis is a sight-threatening ocular inflammatory disorder. Immunological inflammation is regarded as the key to pathogenesis in autoimmune uveitis. Baicalin, the major bioactive component of Scutellaria baicalensis, possesses immunomodulatory properties. However, the role of baicalin in uveitis and its underlying mechanisms remain unclear. In the current study, we found that baicalin treatment obviously inhibited the intraocular inflammatory process in mice with experimental autoimmune uveitis, along with clear declines in infiltrated inflammatory cells and inflammatory cytokine transcription in the retina and draining lymph nodes. Furthermore, baicalin treatment increased the frequency and number of regulatory T cells and decreased the frequency and number of effector T cells (Th1 and Th17 cells) in the draining lymph nodes of mice with experimental autoimmune uveitis. In vitro, baicalin treatment suppressed interphotoreceptor retinoid binding protein-specific CD4+ T cell proliferation and converted CD4+ T cell differentiation. Furthermore, the expression of aryl hydrocarbon receptor was activated by baicalin treatment. Baicalin-mediated modulation of CD4+ T cell differentiation was partially abrogated by the suppression of aryl hydrocarbon receptor. These findings suggest that baicalin modulates the Treg/Teff balance and CD4+ T cell proliferation to ameliorate experimental autoimmune uveitis by activating the aryl hydrocarbon receptor.

Keywords: Aryl hydrocarbon receptor; Baicalin; Teff; Treg; Uveitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Aryl Hydrocarbon / immunology
  • Receptors, Aryl Hydrocarbon / metabolism*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Uveitis / drug therapy*
  • Uveitis / immunology
  • Uveitis / pathology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Flavonoids
  • Receptors, Aryl Hydrocarbon
  • baicalin