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PATTERN RECOGNITION RECEPTORS

Regulation of endosomal TLRs

Nature Reviews Immunology volume 19, pages 660–661 (2019)Cite this article

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Nucleic acid-sensing Toll-like receptors — such as TLR3, TLR7 and TLR9 — are tightly regulated to prevent autoimmune responses to self DNA and RNA. An important feature of this regulation is the intracellular compartmentalization of these TLRs to endosomes, mediated by the chaperone UNC93B1. However, evidence from mouse models that TLR7 and TLR9 can have opposing effects in autoimmune diseases has suggested that there may also be distinct regulatory mechanisms for the individual endosomal TLRs. Two papers in Nature from the group of Gregory Barton report the results of a scanning-alanine mutagenesis screen of UNC93B1 that identifies distinct UNC93B1-dependent mechanisms for the regulation of TLR7 and TLR9.

These results suggested that TLR9 must dissociate from UNC93B1 upon reaching endosomes to enable ligand binding. To independently test this model, the authors artificially tethered TLR9 and UNC93B1 with an intermolecular disulfide bond. The linked proteins trafficked normally to endosomes but TLR9 signalling was completely abrogated.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Kirsty Minton

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  1. Kirsty Minton
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Correspondence to Kirsty Minton.

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Minton, K. Regulation of endosomal TLRs. Nat Rev Immunol 19, 660–661 (2019). https://doi.org/10.1038/s41577-019-0229-1

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