γδ T Cells in Autoinflammatory Diseases

Area of Science:

• Immunology
• Innate Immunity
• T cell Biology

Background:

• Autoinflammatory diseases involve inappropriate innate immune activation without infection.
• Gamma delta (γδ) T cells bridge innate immunity and adaptive functions.
• While neutrophils and macrophages are known drivers, γδ T cells are increasingly recognized as key players.

Purpose of the Study:

• To review the role of γδ T cells in monogenic and multifactorial autoinflammatory diseases.
• To highlight how γδ T cells link innate immune activation to inflammatory pathology.
• To explore the potential of targeting γδ T cells for therapeutic strategies.

Main Methods:

• Review of existing evidence on γδ T cell involvement in various autoinflammatory conditions.
• Analysis of studies examining γδ T cell frequencies, activation, and cytokine profiles.
• Inclusion of transcriptomic and tissue-based analyses of γδ T cells at inflammatory sites.

Main Results:

• γδ T cells show altered frequencies, activation states, and cytokine polarization in diseases like familial Mediterranean fever, gout, and Behçet's disease.
• In inflammasome-driven diseases, γδ T cells often skew towards Interleukin-17 (IL-17) production, enhancing inflammation.
• γδ T cells accumulate and specialize at sites of sterile inflammation, acting as amplifiers.

Conclusions:

• γδ T cells are central amplifiers and modulators of inappropriate innate immune activation in autoinflammatory diseases.
• Their altered function contributes to tissue-specific inflammatory pathology.
• Understanding γδ T cell subset regulation may lead to novel therapeutic approaches.