IL-17 Pathway

The interleukin-17 family of cytokines — central to chronic inflammation and autoimmunity. Discussed extensively by Alistair Henry at Session I in the context of bimekizumab.

Key Biology

• Five isoforms: IL-17A, B, C, D, E (IL-25), F
• IL-17A and IL-17F signal through receptors IL-17RA and IL-17RC
• In human peripheral blood under chronic inflammation: IL-17A initiates the inflammatory response; IL-17F drives the late phase
• This temporal pattern is absent in mouse — a critical species difference

Why IL-17F Matters

• Traditional IL-17A-only inhibitors (secukinumab, ixekizumab) miss the IL-17F contribution
• Bimekizumab was designed to block both A and F — the human data justified the dual-specificity approach
• Back-translation from bimekizumab-treated patients revealed that IL-23 sits upstream of IL-17A/F in a way that complicates the textbook “waterfall” model

Cross-References

• IL-23 — upstream regulator, potentially more complex relationship than previously modeled
• Human pathobiology — the IL-17A/F story is a paradigmatic example of mouse-vs-human divergence
• Psoriasis — primary indication for bimekizumab