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<p>To characterize the complexity of the CD4⁺ T cell compartment in patients with systemic lupus erythematosus (SLE), we performed single-cell RNA sequencing of sorted blood CD4⁺ T cells from pediatric patients and healthy donors. We identified naive, memory, regulatory T (T<sub>reg</sub>) cell, proliferative and interferon-stimulated gene-high (ISG-high) clusters. Within the memory compartment, both follicular and peripheral helper cells were expanded in patients with lupus nephritis and/or high disease activity. Cytotoxic signatures were enriched in effector memory T cells re-expressing CD45RA (TEMRA), as well as in two memory subclusters, one of which overlapped with T helper 10-like cells (T<sub>H</sub>10). Notably, we observed an expansion of dysfunctional T<sub>reg</sub> cells in patients with lupus nephritis, along with upregulation of <i>TLR5</i> and <i>FCRL3</i> in SLE-naive T<sub>reg</sub> cells, suggesting a potential link with mucosal microbial dysbiosis. These findings highlight distinct CD4⁺ T cell subsets that may contribute to aberrant antibody responses and impaired immune regulation in SLE.</p>

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Single-cell RNA profiling of blood CD4+ T cells identifies distinct helper and dysfunctional regulatory clusters in children with SLE

  • 期刊论文

  • 发表日期：

    2025年10月21日

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  • Preetha Balasubramanian,
  • Uthra Balaji,
  • Marina Silva Santos,
  • Jeanine Baisch,
  • Cynthia Smitherman,
  • Lynnette Walters,
  • Paola Sparagana,
  • Lorien Nassi,
  • Katie Stewart,
  • Julie Fuller,
  • Terry Means,
  • Virginia Savova,
  • Jacques F. Banchereau,
  • Tracey Wright,
  • Virginia Pascual,
  • Jinghua Gu,
  • Simone Caielli

摘要

To characterize the complexity of the CD4⁺ T cell compartment in patients with systemic lupus erythematosus (SLE), we performed single-cell RNA sequencing of sorted blood CD4⁺ T cells from pediatric patients and healthy donors. We identified naive, memory, regulatory T (Treg) cell, proliferative and interferon-stimulated gene-high (ISG-high) clusters. Within the memory compartment, both follicular and peripheral helper cells were expanded in patients with lupus nephritis and/or high disease activity. Cytotoxic signatures were enriched in effector memory T cells re-expressing CD45RA (TEMRA), as well as in two memory subclusters, one of which overlapped with T helper 10-like cells (TH10). Notably, we observed an expansion of dysfunctional Treg cells in patients with lupus nephritis, along with upregulation of TLR5 and FCRL3 in SLE-naive Treg cells, suggesting a potential link with mucosal microbial dysbiosis. These findings highlight distinct CD4⁺ T cell subsets that may contribute to aberrant antibody responses and impaired immune regulation in SLE.