The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes

Ivo Rimann, Rosana Gonzalez-Quintial, Roberto Baccala, William B. Kiosses, John R. Teijaro, Christopher G. Parker, Xiaohong Li, Bruce Beutler, Dwight H. Kono, Argyrios N. Theofilopoulos

Research output: Contribution to journalArticlepeer-review

Abstract

SignificanceA large body of evidence has indicated that recognition of self-nucleic acids by endosomal toll-like receptors (TLRs) is central to the pathogenesis of lupus-like systemic autoimmunity in spontaneous mouse models, and the solute carrier SLC15A4 is required for this recognition. Here we describe a mechanism in which SLC15A4 is a major contributor to the proper trafficking of TLRs and their ligands to endolysosomes, wherein recognition and signaling is initiated. This finding supports ongoing efforts to identify pharmacologic inhibitors for this carrier as a means to treat lupus and other inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)e2200544119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number14
DOIs
StatePublished - Apr 5 2022

Keywords

  • AP-3
  • IFN-I
  • lupus
  • nucleic acid–sensing TLRs
  • SLC15 solute carriers

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes'. Together they form a unique fingerprint.

Cite this