IL-23 promotes maintenance but not commitment to the Th17 lineage

Area of Science:

• Immunology
• Cell Biology

Background:

• Interleukin-23 (IL-23) is crucial for inflammatory immunity and IL-17 production.
• The precise mechanisms by which IL-23 exerts its functions have remained unclear.

Purpose of the Study:

• To elucidate the role of IL-23 in maintaining the IL-17-secreting phenotype of T helper 17 (Th17) cells.
• To investigate whether IL-23 promotes commitment to an IL-17-secreting lineage.

Main Methods:

• Utilized an IL-17-capture technique to analyze purified IL-17-secreting cells.
• Performed multiple rounds of in vitro stimulation with IL-23, IL-1beta, and Th1/Th2-inducing cytokines.

Main Results:

• IL-23 maintains the IL-17-secreting phenotype of Th17 cells without impacting cell expansion or survival.
• The Th17 phenotype is most efficiently maintained by IL-23 in combination with IL-1beta.
• Th17 cells lose their IL-17-secreting profile when exposed to Th1 or Th2 cytokines, indicating instability.

Conclusions:

• IL-23 is effective at maintaining the Th17 cell phenotype but does not induce stable lineage commitment.
• The Th17 phenotype is plastic and can be repressed by alternative cytokine environments, unlike Th1 or Th2 cells.