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

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. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Hong-Guo Hu, Pu-Guang Chen, Guanyu Wang, Jun-Jun Wu, Bo-Dou Zhang, Wen-Hao Li, Rebecca L Davis, Yan-Mei Li. Regulation of Immune Activation by Optical Control of TLR1/2 Heterodimerization. Chembiochem : a European journal of chemical biology. 2020 Apr 17;21(8):1150-1154

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PMID: 31702879

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