HMGB1 regulates Th17 cell differentiation and function in patients with psoriasis

Area of Science:

• Immunodermatology
• Molecular mechanisms of inflammatory diseases
• Autoimmune disorders

Background:

• Psoriasis is a chronic inflammatory skin disease driven by T helper 17 (Th17) cells and interleukin-17A (IL-17A).
• High mobility group box 1 (HMGB1) is upregulated in psoriasis and implicated in inflammation.
• The HMGB1-TLR4-IL-23-IL-17A pathway's role in psoriasis pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the role of the HMGB1-TLR4-IL-23-IL-17A pathway in psoriasis.
• To elucidate HMGB1's regulatory mechanism in Th17 cell differentiation.

Main Methods:

• Quantified serum levels of HMGB1, TLR4, IL-23, and IL-17A in 50 psoriasis patients and 30 controls.
• Stimulated peripheral blood mononuclear cells from 10 severe psoriasis patients with recombinant HMGB1 (rHMGB1) in vitro.
• Assessed Th17 cell percentage, mRNA, and protein levels of TLR4, IL-23, IL-17A, and RORγt.

Main Results:

• Psoriasis patients exhibited significantly higher serum HMGB1, TLR4, IL-23, and IL-17A levels than controls, correlating with disease severity.
• In vitro, rHMGB1 dose-dependently increased Th17 cell percentage and expression of TLR4, IL-23, IL-17A, and RORγt.
• Positive correlations were observed between HMGB1, TLR4, IL-23, and IL-17A levels.

Conclusions:

• HMGB1 drives psoriasis pathogenesis by promoting Th17 cell differentiation via the HMGB1-TLR4-IL-23-RORγt pathway.
• This pathway leads to increased IL-17A production and inflammation.
• Targeting HMGB1 presents a potential therapeutic strategy for psoriasis immunotherapy.