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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)288-297
Number of pages10
JournalJournal of Infectious Diseases
Volume217
Issue number2
DOIs
StatePublished - 15 Jan 2018
Externally publishedYes

Keywords

  • T-cell
  • aryl hydrocarbon receptor
  • inflammation
  • superantigen
  • toxic shock

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