Complement component C3 mediates Th1/Th17 polarization in human T-cell activation and cutaneous GVHD

Area of Science:

• Immunology
• Complement System Biology

Background:

• The complement system, particularly C3, regulates T-cell activation and Graft-versus-Host Disease (GVHD).
• C3 influences Th1/Th17 polarization in mouse models of GVHD.

Purpose of the Study:

• To investigate the impact of anticomplement therapy on human T-cell activation.
• To evaluate the role of C3 in human cutaneous GVHD.

Main Methods:

• Inhibition of C3 activation using the drug candidate Compstatin.
• Analysis of cytokine production (IFN-γ, IL-4, IL-17, IL-2, TNF-α) in activated CD4+ T cells.
• Assessment of T-cell proliferation (CD4+ and CD8+) upon TCR stimulation.
• Examination of complement deposition in skin and lip biopsies from GVHD patients.

Main Results:

• Compstatin significantly reduced the frequency of IFN-γ, IL-4, IL-17, IL-2, and TNF-α producing cells in activated CD4+ T cells.
• Compstatin decreased proliferation of both CD4+ and CD8+ T cells but did not affect IL-2/TNF-α production or CD8+ T cell differentiation.
• C3 deposition was observed in GVHD patient skin biopsies, correlating with gland damage and regeneration.

Conclusions:

• C3 mediates Th1/Th17 polarization in human T-cell activation.
• C3 plays a significant role in the pathogenesis of human cutaneous GVHD.
• Anticomplement therapy targeting C3 warrants further investigation for GVHD treatment.