Properties and origin of human Th17 cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Distinct CD4+ T-cell subsets, including Th1, Th2, and Th17, have been identified based on cytokine production.
• Murine Th17 cells are crucial for defense against pathogens and implicated in autoimmune diseases, though their role is debated.
• Human Th17 cells exhibit unique characteristics compared to their murine counterparts, impacting our understanding of immune responses.

Purpose of the Study:

• To elucidate the distinct features and developmental pathways of human Th17 cells.
• To compare and contrast human and murine Th17 cell characteristics.
• To re-evaluate the roles of Th17 and Th1 cells in autoimmune pathogenesis.

Main Methods:

• Flow cytometry analysis of human Th17 cell surface markers (CCR6, IL-23R, IL-12Rbeta2, CD161).
• Intracellular cytokine staining to assess IFN-gamma and IL-17A production.
• In vitro differentiation assays using various cytokines (IL-1beta, IL-23, TGF-beta, IL-6, IL-12) to study human Th17 cell development.

Main Results:

• Human Th17 cells express CCR6, IL-23R, IL-12Rbeta2, and CD161.
• Human Th17 cells can produce both IL-17A and IFN-gamma, influenced by IL-12, and express T-bet and RORgammat.
• Human Th17 differentiation is driven by IL-1beta and IL-23, with TGF-beta promoting expansion rather than differentiation, unlike in mice.

Conclusions:

• Human Th17 cells possess a distinct developmental trajectory and functional plasticity compared to murine Th17 cells.
• The plasticity of human Th17 cells, including potential to produce IFN-gamma, suggests a closer relationship with Th1 cells.
• These findings necessitate a revised understanding of Th17 cell involvement in human autoimmune and inflammatory diseases.