Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases

Kensuke Miyake; Takuma Shibata; Ryutaro Fukui; Yusuke Murakami; Ryota Sato; Ryosuke Hiranuma

doi:10.1007/978-981-99-9781-7_7

Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases

Adv Exp Med Biol. 2024:1444:97-108. doi: 10.1007/978-981-99-9781-7_7.

Authors

Kensuke Miyake¹, Takuma Shibata², Ryutaro Fukui², Yusuke Murakami³, Ryota Sato², Ryosuke Hiranuma²

Affiliations

¹ Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kmiyake@ims.u-tokyo.ac.jp.
² Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
³ Faculty of Pharmacy, Department of Pharmaceutical Sciences and Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.

PMID: 38467975
DOI: 10.1007/978-981-99-9781-7_7

Abstract

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) reside in the endosomal compartment of innate immune cells, such as macrophages and dendritic cells. NAs transported to the endosomal compartment are degraded by DNases and RNases. Degradation products, including single-stranded DNA, oligoRNA, and nucleosides, are recognized by TLR7, TLR8, and TLR9 to drive the defense responses against pathogens. NA degradation influences endosomal TLR responses by generating and degrading TLR ligands. TLR ligand accumulation because of impaired NA degradation causes constitutive TLR activation, leading to autoinflammatory and autoimmune diseases. Furthermore, some genes associated with these diseases promote endosomal TLR responses. Therefore, endosomal TLRs are promising therapeutic targets for TLR-mediated inflammatory diseases, and novel drugs targeting TLRs are being developed.

Keywords: DNase; Monogenic disease; RNase; SLC29A3; Toll-like receptor.

MeSH terms

Autoimmune Diseases* / drug therapy
Humans
Macrophages / metabolism
Nucleic Acids* / metabolism
Toll-Like Receptors

Substances

Toll-Like Receptors
Nucleic Acids