Th 17 Cells and Arthritis

Before, the choice for intervening in the IL-17 pathway appeared easier, with one ligand, IL-17, and one receptor, IL-17R, to target. Today, the options have increased with the other members of the IL-17 family, which include IL-17A to IL-17F. The IL-17 receptor family has also expanded, with IL-17RA and IL-17RC being critical for the action of IL-17A and IL-17F.

As of today, a demonstration of the beneficial effect of IL-17 inhibition is yet to be obtained in the clinic. Limitations for targeting as a therapy IL-17 could be the low bioactivity of IL-17—at least when used alone—the reduced numbers of IL-17–secreting cells in RA synovium, and the overlap with the effects of TNF. Thus, the position of IL-17 inhibition in the hierarchy of RA therapy is still unclear. In addition, planning RA clinical trials is often affected by tradition. For agencies today, the goal is to be equal or superior to TNF inhibitors. If this practice is followed, then patients resistant to TNF inhibitors will have to be enrolled in initial trials of an anti–IL-17 inhibition. In contrast, trials would need a different design if control of chronicity and induction of repair are the primary endpoints.

Conclusion

The story from the inside shows that basic research can inspire disease-related research, that the development of new therapeutics can be slow and complicated when patent issues are involved, and that the pursuit of fashionable research may not always be productive. This story is also about friendship—it’s been 20 years since Wim, Gary, and I edited our textbook together. Science can be a way to enjoy life, and many of my best research ideas have come from times when I’ve shared a beer with Wim and Gary or, from the comfort of a sandy beach, I’ve watched Gary surf. I look forward to many more years of science and friendship with my colleagues and I wonder how, 20 years from now, we will look at the renewed interest in cells whose importance was once seriously doubted.

Dr. Miossec is professor of immunology and rheumatology at the Hôpital Edouard Herriot in Lyon, France.

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