Autoimmune memory T helper 17 cell function and expansion are dependent on interleukin-23

Area of Science:

• Immunology
• Neuroimmunology
• Autoimmunity

Background:

• Interleukin-23 (IL-23) is critical for pathogenic T helper 17 (Th17) cell differentiation.
• The role of IL-23 in memory Th17 cell responses remains largely undefined.

Purpose of the Study:

• To investigate the function of IL-23 in memory Th17 cell responses within the experimental autoimmune encephalomyelitis (EAE) model.
• To elucidate the mechanisms by which IL-23 influences Th17 cell recall responses and disease pathogenesis.

Main Methods:

• Utilized the EAE mouse model to study Th17 cell memory responses.
• Analyzed Th17 cell phenotype, proliferation, and transcription factor expression (RORγt, T-bet) following rechallenge.
• Investigated the impact of IL-23 receptor blockade on Th17 cell function and disease course.

Main Results:

• Memory Th17 cells expanded robustly upon rechallenge, migrating to the CNS and exacerbating EAE.
• IL-23 was essential for this enhanced recall response, influencing Th17 cell proliferation and generation of T-bet coexpressing effectors.
• IL-23 signaling regulated cell-cycle progression genes in Th17 cells, indicating a key role in proliferation.

Conclusions:

• IL-23 is crucial for the expansion and effector function of memory Th17 cells in autoimmune settings.
• IL-23 signaling primarily impacts Th17 cell responses by regulating proliferation and effector differentiation.
• Targeting IL-23 may offer therapeutic potential for autoimmune diseases driven by Th17 memory responses.