Data · dataset · 2023
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders
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Loss-of-function mutations in the lysosomal nucleoside transporter SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs.
Description
However, little is known about the mechanism by which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis in Slc29a3–/– mice was shown to depend on Toll-like receptor 7 (TLR7), which senses a combination of nucleosides and oligoribonucleotides (ORNs).
TLR7 increased phagocyte numbers by driving the proliferation of Ly6Chi immature monocytes and their maturation into Ly6Clow phagocytes in Slc29a3–/– mice. Downstream of TLR7, FcRγ and DAP10 were required for monocyte proliferation. Histiocytosis is accompanied by inflammation in SLC29A3 disorders.
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However, TLR7 in nucleoside-laden splenic macrophages failed to activate inflammatory responses. Enhanced production of pro-inflammatory cytokines was observed only after stimulation with ssRNAs, which would increase lysosomal ORNs. Patient-derived monocytes harboring the G208R SLC29A3 mutation showed enhanced survival and proliferation in a TLR8 antagonist-sensitive manner.
These results demonstrated that TLR7/8 responses to lysosomal nucleoside stress drive SLC29A3 disorders.
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Where it is published
- Repository landing page datadryad.org/dataset/doi:10.5061/dryad.j0zpc86kn ↗
landing page · from DataCite
- DOI doi.org/10.5061/dryad.j0zpc86kn ↗
DOI / persistent id · from DataCite
Documentation and papers
- Creative Commons Zero v1.0 Universal creativecommons.org/publicdomain/zero/1.0/legalcode ↗
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- IsCitedBy 10.1101/2022.10.27.513971 doi.org/10.1101/2022.10.27.513971 ↗
publication · from DataCite
- IsCitedBy 10.1084/jem.20230054 doi.org/10.1084/jem.20230054 ↗
publication · from DataCite
Catalogue records · 2
- DataCite API api.datacite.org/dois/10.5061/dryad.j0zpc86kn ↗
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- DataCite Commons commons.datacite.org/doi.org/10.5061/dryad.j0zpc86kn ↗
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Topics
- Stated by source
- Basic medicine
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| DataCite | 10.5061/dryad.j0zpc86kn | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| byte_size | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].fos:basic-medicine | source · DataCite | connector:datacite@1.0.0 | |
| created_date | source · DataCite | connector:datacite@1.0.0 | |
| description | source · DataCite | connector:datacite@1.0.0 | /data/attributes/descriptions |
| license | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| publication_date | source · DataCite | connector:datacite@1.0.0 | /data/attributes/dates |
| title | source · DataCite | connector:datacite@1.0.0 | /data/attributes/titles/0/title |
| updated_date | source · DataCite | connector:datacite@1.0.0 | |
| version_label | source · DataCite | connector:datacite@1.0.0 |