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Omics · study · 2026

Single-cell transcriptomes and T cell receptor sequences of CD4 or CD8 single positive T lymphocytes from peripheral blood or urine of lupus nephritis patients at flare.

Listed in NCBI GEO

Proliferative lupus nephritis (LN) is triggered by deposition of autoantibodies in glomeruli and paralleled by a T cell-rich kidney infiltrate.

Description

Although these T cells have been attributed with propagation of tissue injury, it is unclear how they are activated and whether T cell autoreactivity drives the local inflammation. Kidney-infiltrating T cells are also observed in urine, where they have high resemblance with interstitial T cells.

Therefore, urinary T cells are a proxy to investigate tissue pathogenesis. Here, we analyzed urinary T cells to elucidate if a kidney-specific T cell autoimmune reaction contributes to tubulointerstitial inflammation in LN. Using single cell RNA sequencing, we compared transcriptomes and clonotypes of T cells from blood and urine of patients with active LN and show that urinary T cells were mostly activated CD8 effector memory cells recruited from a circulating CX3CR1+ subset.

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Several urinary CD8 T cell clones were expanded. However, upon in vitro testing of their T cell receptors, we did not observe autoreactivity against autologous tubular epithelial cells. Instead, approximately 20% of expanded clonotypes were Epstein-Barr virus- or cytomegalovirus specific, but respective viral antigens were undetectable in kidney biopsies or urine.

Conversely, kidney-infiltrating T cells had access to interleukin-15 and interferon (IFN) β and stimulation with these cytokines was sufficient to trigger degranulation and production of tumor necrosis factor, IFN γ and granzyme K. Together, these results show that CD8+CX3CR1+ T cells are recruited into the kidney in LN, where they are activated by cytokines enabling them to contribute to local inflammation.

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Life Sciences
Inferred from text
Cancer 65% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE32252710 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title