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

doi:10.1073/pnas.2200544119

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 journal › Article › peer-review

2 Scopus citations

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 language	English (US)
Pages (from-to)	e2200544119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	14
DOIs	https://doi.org/10.1073/pnas.2200544119
State	Published - Apr 5 2022

Keywords

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

ASJC Scopus subject areas

General

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10.1073/pnas.2200544119

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Rimann, I., Gonzalez-Quintial, R., Baccala, R., Kiosses, W. B., Teijaro, J. R., Parker, C. G., Li, X., Beutler, B., Kono, D. H., & Theofilopoulos, A. N. (2022). The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes. Proceedings of the National Academy of Sciences of the United States of America, 119(14), e2200544119. https://doi.org/10.1073/pnas.2200544119

The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes. / Rimann, Ivo; Gonzalez-Quintial, Rosana; Baccala, Roberto et al.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 14, 05.04.2022, p. e2200544119.

Research output: Contribution to journal › Article › peer-review

Rimann, I, Gonzalez-Quintial, R, Baccala, R, Kiosses, WB, Teijaro, JR, Parker, CG, Li, X , Beutler, B, Kono, DH & Theofilopoulos, AN 2022, 'The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 14, pp. e2200544119. https://doi.org/10.1073/pnas.2200544119

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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.",

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AU - Kiosses, William B.

AU - Teijaro, John R.

AU - Parker, Christopher G.

AU - Li, Xiaohong

AU - Beutler, Bruce

AU - Kono, Dwight H.

AU - Theofilopoulos, Argyrios N.

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

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Keywords

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