S101, an Inhibitor of Proliferating T Cells, Rescues Mice From 
Superantigen-Induced Shock

Shir, Alexei; Klein, Shoshana; Sagiv-Barfi, Idit; Geiger, Tamar; Zigler, Maya; Langut, Yael; Edinger, Nufar; Levitzki, Alexander

doi:10.1093/infdis/jix576

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S101, an Inhibitor of Proliferating T Cells, Rescues Mice From Superantigen-Induced Shock

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Geiger, Tamar
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Shir, A., Klein, S., Sagiv-Barfi, I., Geiger, T., Zigler, M., Langut, Y., et al. (2018). S101, an Inhibitor of Proliferating T Cells, Rescues Mice From Superantigen-Induced Shock. Journal of Infectious Diseases, 217(2), 288-297. doi:10.1093/infdis/jix576.

Cite as: https://hdl.handle.net/21.11116/0000-0003-121E-8

Abstract

Superantigens (SAgs) are extremely potent bacterial toxins, which evoke a virulent immune response, inducing nonspecific T-cell proliferation, rapid cytokine release, and lethal toxic shock, for which there is no effective treatment. We previously developed a small molecule, S101, which potently inhibits proliferating T cells. In a severe mouse model of toxic shock, a single injection of S101 given together with superantigen challenge rescued 100% of the mice. Even when given 2 hours after challenge, S101 rescued 40% of the mice. S101 targets the T-cell receptor, inflammatory response, and actin cytoskeleton pathways. S101 inhibits the aryl hydrocarbon receptor, a ligand-activated transcription factor that is involved in the differentiation of T-helper cells, especially Th17, and regulatory T cells. Our results provide the rationale for developing S101 to treat superantigen-induced toxic shock and other pathologies characterized by T-cell activation and proliferation.