Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells

Area of Science:

• Immunology
• Endocrinology
• Cell Biology

Background:

• Adiponectin is a key immunomodulatory mediator in inflammation.
• Adiponectin receptor 1 (AdipoR1) expression was previously confirmed in murine regulatory T cells (Tregs).
• The expression and function of AdipoR1 in human Tregs remained uncharacterized.

Purpose of the Study:

• To investigate AdipoR1 expression in human Tregs.
• To determine the effect of globular adiponectin (gAd) on human Treg IL-10 secretion.
• To explore the role of Type 2 (T2) inflammation in modulating AdipoR1-mediated Treg function.

Main Methods:

• Human Tregs were analyzed for AdipoR1, Helios, and IL-10 expression using flow cytometry.
• CD4+ T cells were cultured with gAd, AdipoRon (an AdipoR1 agonist), or T2 cytokines.
• Intracellular cytokine levels, cell surface markers, and signaling pathway activation (p38 MAPK) were assessed.

Main Results:

• A subset of human Tregs expressed AdipoR1, with higher expression observed in Helios-negative Tregs.
• gAd and AdipoRon treatment significantly increased IL-10 secretion, FOXP3 expression, and p38 MAPK phosphorylation in Helios-negative AdipoR1-positive Tregs.
• T2 inflammation amplified gAd-induced IL-10 production, particularly in Helios-positive AdipoR1-positive Tregs.

Conclusions:

• The adiponectin/AdipoR1 axis enhances IL-10 release by human Tregs, primarily in the Helios-negative subset.
• Type 2 inflammation potentiates the IL-10 secretory function of AdipoR1-expressing Tregs, especially in the Helios-positive subset.
• These findings suggest a novel mechanism by which adiponectin influences Treg-mediated immune responses in inflammatory settings.