Decay-accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic-induced autoimmunity

Area of Science:

• Immunology
• Autoimmunity
• Molecular Biology

Background:

• Decay-accelerating factor 1 (Daf1) absence enhances T-cell responses and autoimmunity, notably via interferon-gamma (IFN-γ) upregulation.
• Murine mercury-induced autoimmunity (mHgIA) is an IFN-γ-dependent autoimmune model.

Purpose of the Study:

• To investigate if Daf1 deficiency exacerbates IFN-γ-dependent mHgIA.
• To analyze the impact of Daf1 deficiency on cytokine expression, T-cell activation, and humoral autoimmunity.

Main Methods:

• C57/BL6 Daf1(+/+) and Daf1(-/-) mice were exposed to mercuric chloride (HgCl2).
• Cytokine expression, T-cell activation, and autoantibody levels (IgG, ANAs, anti-chromatin) were assessed.
• In vitro studies involved CD4+ T-cell stimulation with anti-CD3/anti-CD28 and Daf1/CD97 interactions.

Main Results:

• Daf1 deficiency exacerbated mHgIA, increasing serum IgG, ANAs, and anti-chromatin autoantibodies.
• Aggravated autoimmunity was linked to elevated IFN-γ, IL-2, IL-4, and IL-10, but not IL-17.
• In vitro T-cell stimulation showed altered cytokine profiles, suggesting mercury's role in Daf1-deficient mice.
• Daf1 and CD97 interaction modulated mHgIA-associated cytokine expression (increased IL-10, decreased IL-17, IL-21, IFN-γ).

Conclusions:

• Absence of Daf1 worsens mercury-induced autoimmunity with distinct cytokine profile changes.
• Daf1-CD97 interaction influences key cytokines in autoimmunity, suggesting a therapeutic target for controlling excessive cytokine production.