Regulation of Immune Activation by Optical Control of TLR1/2 Heterodimerization

Chembiochem. 2020 Apr 17;21(8):1150-1154. doi: 10.1002/cbic.201900591. Epub 2020 Jan 20.

Abstract

The activation of toll-like receptors (TLRs) plays important roles in the immune response. The ability to control the activities of TLRs could be usable as a switch for immune response. Here we have rationally designed and synthesized a photoswitchable Pam3 CSK4 derivative-P10-to control the activation of TLR1/2. The ground-state trans-P10 was able to stimulate and activate antigen-presenting cells (APCs) by promoting TLR1/2 heterodimerization. However, cis-P10, derived from UV irradiation of trans-P10, reduced the activities of APCs by impeding the TLR1/2 heterodimerization. In the absence of UV radiation, the cis-P10 slowly returned to its ground trans state, restoring the activities of the APCs stimulation. Our results indicated that optical control of TLR1/2 heterodimerization mediated by the photoswitchable P10 offers the potential to regulate immune activation and inflammation.

Keywords: TLR1/2; azobenzenes; dimerization; immunochemistry; photoswitching.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Humans
  • Immunity / immunology*
  • Lipopeptides / pharmacology*
  • Mice
  • Protein Multimerization*
  • RAW 264.7 Cells
  • Signal Transduction
  • THP-1 Cells
  • Toll-Like Receptor 1 / agonists*
  • Toll-Like Receptor 1 / chemistry
  • Toll-Like Receptor 2 / agonists*
  • Toll-Like Receptor 2 / chemistry
  • Ultraviolet Rays*

Substances

  • Lipopeptides
  • Pam(3)CSK(4) peptide
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2