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Jill F Wright, Frann Bennett, Bilian Li, Jonathan Brooks, Deborah P Luxenberg, Matthew J Whitters, Kathleen N Tomkinson, Lori J Fitz, Neil M Wolfman, Mary Collins, Beatriz M Carreno, Kyri Dunussi-Joannopoulos, Moitreyee Chatterjee-Kishore, The functional activity of human IL-17A, IL-17F and IL-17A/IL-17F cytokines is dependent on the receptors IL-17R and IL-17RC (94.31), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S176, https://doi.org/10.4049/jimmunol.178.Supp.94.31
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Abstract
IL-17A and IL-17F are members of the IL-17 cytokine family and have been detected in tissue samples from patients with autoimmune disease. Recent data has shown that these cytokines are secreted by a new CD4+ T cell lineage known as Th17 cells. We have recently demonstrated that activated human CD4+ T cells also produce the IL-17A/IL-17F heterodimer with in vitro functional activity. Both IL-17R and IL-17RC are required for activity of IL-17A and IL-17F. However, the question remains whether IL-17A/IL-17F also utilizes the same receptors for activity or whether it signals through different receptor chains. ELISA and BiaCore-based binding experiments were performed to determine if IL-17A/IL-17F could bind to IL-17R and IL-17RC. We find that IL-17A, IL-17F and IL-17A/IL-17F each bind to IL-17R but with different affinities, whereas they bind to IL-17RC with comparable affinity. Using cell based assays, we have evaluated the functional activity of IL-17A, IL-17F and IL-17A/IL-17F in the presence of soluble receptors, antibodies to the receptors and IL-17R and IL-17RC siRNA. We find that the activity of IL-17A, IL-17F and IL-17A/IL-17F is decreased when the expression of IL-17R is reduced, whereas the activity of the cytokines decreases to a lesser extent when the expression of IL-17RC is reduced. In conclusion, our results suggest that IL-17A, IL-17F and IL-17A/IL-17F each bind and signal through the same receptor complex.