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 Pam3CSK4 derivative—P10—to control the activati...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2020-04, Vol.21 (8), p.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: Article
Language:English
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
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Summary: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.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201900591