Constarium
← Search

Omics · dataset · 2026

Data Sheet 1_PD-1 deficiency reshapes the TCRβ repertoire and T-cell developmental programs associated with susceptibility to lupus-like autoimmunity.pdf

Listed in figshare

Introduction<p>Programmed cell death protein-1 (PD-1) functions as a pivotal immune checkpoint, essential for maintaining peripheral immune tolerance, and serves as a significant therapeutic target in cancer immunotherapy.

Description

Nevertheless, the relationship between PD-1 deficiency and baseline alterations in T-cell receptor (TCR) repertoire organization, as well as the susceptibility to lupus-like autoimmunity, remains inadequately elucidated.</p>Methods<p>In this study, we integrated immune repertoire sequencing with bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) to delineate the organization of the TCRβ repertoire and genotype-associated transcriptional changes in PD-1-deficient mice.

To assess autoimmune susceptibility following an environmental immune challenge, we utilized a Campylobacter jejuni (CJ-S131)-induced lupus-like autoimmune model.</p>Results<p>Our findings revealed that PD-1-deficient mice exhibited alterations in TCRβ repertoire diversity, complementarity-determining region 3 (CDR3) length distributions, TRBV/TRBJ segment usage, V-D-J recombination patterns, and clonotype abundance. Through transcriptomic analysis, we identified significant alterations in the expression of genes linked to lymphocyte development and the maintenance of the T-cell receptor (TCR) repertoire.

Read the rest (2 more)

Concurrently, our predicted regulatory-network analysis highlighted FOXC1, E2F1, GATA2, and MEF2A as potential upstream transcription factors implicated in subsets of these transcriptional changes. PD-1 deficiency was correlated with modified proportions of T cells, natural killer (NK) cells, B cells, and the CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>low/−</sup> putative regulatory T-cell population. Additionally, PD-1-deficient splenocytes demonstrated heightened proliferative responses upon polyclonal stimulation.

In the context of CJ-S131-induced autoimmune challenge, PD-1-deficient mice exhibited elevated levels of lupus-associated autoantibodies and more severe lupus-like renal pathology.</p>Discussion<p>Collectively, our findings suggest that PD-1 deficiency is linked to disrupted TCRβ repertoire organization, extensive immune dysregulation, and an increased vulnerability to infection-induced lupus-like autoimmunity.</p>

Links

Where it is published

Catalogue records · 1

Topics

Inferred from text
Cancer 75% · Immunology 72% · RNA sequencing 75%
Provenance · 1 source records, 20 field assertions
SourceKeyLast seenRaw
figshareoai:figshare.com:article/3377173610 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · figshare comconnector:figshare_com@1.0.0
concepts[disease].local:disease:cancerenrichment · figshare comkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].anzsrc:group:3204enrichment · figshare comtaxonomy-embedding@1.0.0title+keywords+description (72%)
concepts[field].local:field:astronomymapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:chemistrymapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:computer-science-aimapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:earth-environmentalmapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:economics-financemapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:engineeringmapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:humanitiesmapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:life-sciencesmapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:medicine-healthmapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:ocean-atmosphericmapping · figshare comconnector:figshare_com@1.0.0
concepts[field].local:field:social-sciencemapping · figshare comconnector:figshare_com@1.0.0
concepts[modality].local:modality:rna-seqenrichment · figshare comkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingmapping · figshare comvocabulary-mapper@1.0.0keywords['high-throughput sequencing']
descriptionsource · figshare comconnector:figshare_com@1.0.0/metadata/dc/description
licensesource · figshare comconnector:figshare_com@1.0.0/metadata/dc/rights
publication_datesource · figshare comconnector:figshare_com@1.0.0
titlesource · figshare comconnector:figshare_com@1.0.0/metadata/dc/title