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

• Published in: Chembiochem : a European journal of chemical biology Vol. 21; no. 8; pp. 1150 - 1154
• Main Authors: Hu, Hong‐Guo, Chen, Pu‐Guang, Wang, Guanyu, Wu, Jun‐Jun, Zhang, Bo‐Dou, Li, Wen‐Hao, Davis, Rebecca L., Li, Yan‐Mei
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17-04-2020
• Subjects: Activation; Antigen-presenting cells; Antigens; azobenzenes; dimerization; Immune response; Immune system; immunochemistry; Irradiation; Optical control; photoswitching; Proteins; Stability; TLR1 protein; TLR1/2; Toll-like receptors; Ultraviolet radiation; dimerization; azobenzenes; photoswitching; TLR1/2; immunochemistry
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201900591

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 Pam3CSK4 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.
Reduction of systemic inflammation without immune system inhibition: A photoswitchable ligand for regulation of immune activation through optical control of the heterodimerization of toll‐like receptors 1 and 2 (TLR1/2) has been developed, offering the potential to regulate immune activation and inflammation.