The cytokine IL-6 performs critical functions in various tissue types but is implicated in autoimmune disease. Therefore, precisely targeting the pathway by which IL-6 induces inflammatory immune cell activation could leave other signaling pathways and functions of IL-6 intact. Currently, such targeted molecules lack sufficient selectivity. Heise et al. developed a chimeric molecule that bound to and "trapped" a critical IL-6 trans-signaling protein complex and that was smaller, had greater selectivity for the IL-6 complex over a similar IL-11 complex, and more effectively inhibited the IL-6-induced inflammatory activation of cultured T cells. These findings may lead to improved therapeutics for patients with autoimmune disease.
Highlights
A variety of sgp130Fc muteins was generated.
Introduction of a gp130 SNP (R281Q) into sgp130Fc increases IL-6 specificity.
The sgp130Fc variant sgp130
FlyR
exclusively affects IL-6 trans-signaling.
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