1. Academic Validation
  2. 3,3'-Diindolylmethane inhibits Th17 cell differentiation via impairing IRF-7-mediated plasmacytoid dendritic cell activation in imiquimod-induced psoriasis mice

3,3'-Diindolylmethane inhibits Th17 cell differentiation via impairing IRF-7-mediated plasmacytoid dendritic cell activation in imiquimod-induced psoriasis mice

  • In Vitro Cell Dev Biol Anim. 2024 Apr 11. doi: 10.1007/s11626-024-00901-7.
Mahaboobkhan Rasool 1 Manupati Srikanth 2 Arulkumaran Rithvik 2
Affiliations

Affiliations

  • 1 SMV 240, Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632 014, Tamil Nadu, India. rasool.m@vit.ac.in.
  • 2 SMV 240, Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632 014, Tamil Nadu, India.
Abstract

Psoriasis is a paradigmatic condition characterised by a heightened autoimmune response and chronic inflammation. However, the exact nature and the pathological causes behind it are still unknown. Growing evidence suggest dysregulated cytokine network as a result of over-activated T cells and plasmacytoid dendritic cells (pDCs) as the critical drivers in the development of psoriasis. In the present study, we aimed to investigate the therapeutic efficacy of 3,3'-diindolylmethane (DIM) on pDC activation and Th17 cell development in imiquimod (IMQ)-induced psoriasis mice. Our in vitro research investigated the IRF-7 signalling in pDCs that explained the reduced expression of the transcription factor IRF-7 responsible for pDC activation as a result of DIM treatment. Concurrently, DIM treatment decreased the release of Th17 cell polarising cytokines (IFN-α, IL-23, and IL-6) by pDCs which validated a reduction in differentiated pathogenic Th17 cell population and associated cytokine IL-17A in IMQ-induced psoriatic mice. Thus, our recent findings provide therapeutic evidence in targeting the early potential contributors for psoriasis treatment by preventing IRF-7-mediated pDC activation and Th17 cell development in IMQ-induced psoriasis mice.

Keywords

3,3′-Diindolylmethane, Interferon regulatory factor-7 (IRF-7); Plasmacytoid dendritic cells; Psoriasis; Th17 cells.

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