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
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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.
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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>
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Where it is published
- DOI doi.org/10.3389/fimmu.2026.1911666.s002 ↗
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Catalogue records · 1
- OAI-PMH record api.figshare.com/v2/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Af… ↗
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Topics
- From keywords
- Astronomy & Astrophysics · Chemistry · Computer Science & AI · Earth & Environmental Science · Economics & Finance · Engineering · Humanities · Life Sciences · Medicine & Health · Ocean & Atmospheric Science · Sequencing · Social Science
- Inferred from text
- Cancer 75% · Immunology 72% · RNA sequencing 75%
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