Microbe-Dependent Induction of IL-9 by CLA⁺ T Cells in Psoriasis and Relationship with IL-17A

Area of Science:

• Immunology
• Dermatology
• Cytokine Biology

Background:

• Interleukin-9 (IL-9) is found in psoriatic lesions, produced by lymphocytes.
• The induction of IL-9 by specific psoriasis pathogens like Streptococcus pyogenes remains unclear.

Purpose of the Study:

• To investigate IL-9 production in response to pathogenic triggers in a psoriasis ex vivo model.
• To elucidate the role of IL-9 in the immune response within psoriasis.

Main Methods:

• Utilized a psoriatic ex vivo model to assess cytokine production upon exposure to S. pyogenes and Candida albicans extracts.
• Investigated the interaction between CLA+ T cells and epidermal cells in cytokine induction.
• Employed cytokine neutralization and co-culture systems with patient samples.

Main Results:

• S. pyogenes and C. albicans extracts induced IL-9, IL-17A, and IFN-γ production.
• IL-9 induction was dependent on CLA+ T cell and epidermal cell interactions.
• IL-9 neutralization reduced S. pyogenes-induced IL-17A production but not IFN-γ.
• IL-9 enhanced the survival of circulating psoriatic CLA+ T cells.
• Elevated IL-9 and cytokine responses correlated with disease severity (Psoriasis Area Severity Index) and anti-streptolysin O levels in streptococcal-driven guttate psoriasis.

Conclusions:

• IL-9 promotes psoriasis inflammation by up-regulating IL-17A production.
• Streptococcal-sensitized CLA+ T cells contribute to IL-9-mediated immune responses in psoriasis.
• These findings highlight a significant role for IL-9 in streptococcal-associated guttate psoriasis.