Dallas, October 22, 2025
News Summary
A new study from Dallas examines CD4⁺ T cell subsets in relation to systemic lupus erythematosus (SLE) activity and immune dysfunction in pediatric patients. By utilizing single-cell RNA sequencing, researchers identified various T cell clusters and observed specific expansions tied to lupus nephritis. The findings suggest potential links between T cell dysfunction and microbial dysbiosis, emphasizing the need for targeted therapies to address these immune challenges.
Dallas — A new pediatric study mapped the complexity of the CD4⁺ T cell compartment and identified distinct T cell subsets linked to systemic lupus erythematosus (SLE) activity and immune dysfunction, with specific changes tied to lupus nephritis and high disease activity.
Top-line findings
The study reports that a variety of CD4⁺ T cell clusters were identified, including naive, memory, regulatory T (Treg) cells, proliferative, and interferon-stimulated gene-high (ISG-high) clusters. In patients with lupus nephritis and/or high disease activity, both follicular and peripheral helper T (Tfh) cells were observed to be expanded. Cytotoxic signatures were enriched in effector memory T cells re-expressing CD45RA (TEMRA) and in a subcluster overlapping with T helper 10-like (TH10) cells. The study found an expansion of dysfunctional Treg cells in patients with lupus nephritis. Increased expression of Toll-like receptor 5 (TLR5) and Fc receptor-like 3 (FCRL3) was noted in SLE-naive Treg cells, implying a potential association with microbial dysbiosis.
Methods and scope
Approach
Researchers utilized single-cell RNA sequencing of sorted blood CD4⁺ T cells. Both pediatric patients and healthy donors were included in the study. The single-cell approach allowed researchers to resolve multiple cell clusters and subclusters within the CD4⁺ T cell compartment and to compare patterns related to disease activity and organ involvement.
Sample and validation
The study involved pediatric patients with SLE and healthy control donors to distinguish disease-associated signatures from normal variation. The sorted CD4⁺ T cell dataset and validation cohorts are available for further research.
Why these results matter
This research indicates specific CD4⁺ T cell subsets may contribute to abnormal antibody responses and ineffective immune regulation in SLE. Expansion of follicular and peripheral helper T cell populations can favor stronger or misdirected antibody production, while dysfunctional Treg expansion suggests a weakened system for controlling immune activation. The finding of increased TLR5 and FCRL3 expression in SLE-naive Treg cells points to a possible link with microbial dysbiosis that could influence immune behavior.
Implications for treatment and research
By pinpointing cellular and molecular patterns tied to disease activity and kidney involvement, the study highlights candidate targets for future targeted therapies aimed at correcting dysfunctional CD4⁺ T cell subsets. The availability of the sorted CD4⁺ T cell dataset and validation cohorts supports broader analysis and replication, which can accelerate follow-up studies and therapeutic development.
Funding and acknowledgments
Researchers thank pediatric patients, families, and collaborators at Texas Scottish Rite Hospital for Children and the Children’s Medical Center in Dallas for their contributions. Funding for the study was provided by multiple NIH grants and Sanofi.
Background context
Systemic lupus erythematosus is an autoimmune disease where the immune system attacks the body’s own tissues. In pediatric patients, disease onset and progression can differ from adults, and organ involvement such as lupus nephritis (kidney inflammation) can drive more severe outcomes. CD4⁺ T cells include several functional groups: naive cells that have not yet encountered antigen, memory cells that respond faster to previously seen antigens, helper subsets that guide antibody-producing B cells, and regulatory T (Treg) cells that restrain excessive immune responses. Disruption in the balance among these types can lead to abnormal antibody responses and failed immune regulation—features central to SLE pathophysiology.
Next steps
Researchers recommend further studies that use the available datasets to confirm these patterns across larger and more diverse pediatric populations, to explore causal links between microbial signals and Treg dysfunction, and to evaluate therapeutic strategies that target the identified dysfunctional CD4⁺ T cell subsets to improve patient outcomes.
FAQ
What did the study reveal?
Study Reveals Distinct CD4⁺ T cell Subsets Linked to Systemic Lupus Erythematosus Activity and Dysfunction in Pediatric Patients
What methods did researchers use?
Researchers utilized single-cell RNA sequencing of sorted blood CD4⁺ T cells.
Who was included in the study?
Both pediatric patients and healthy donors were included in the study.
What were the main cellular findings?
A variety of CD4⁺ T cell clusters were identified, including naive, memory, regulatory T (Treg) cells, proliferative, and interferon-stimulated gene-high (ISG-high) clusters.
Which changes were seen in patients with lupus nephritis or high disease activity?
In patients with lupus nephritis and/or high disease activity, both follicular and peripheral helper T (Tfh) cells were observed to be expanded.
Were any dysfunctional regulatory cells observed?
The study found an expansion of dysfunctional Treg cells in patients with lupus nephritis.
What molecular changes were noted in naive Treg cells?
Increased expression of Toll-like receptor 5 (TLR5) and Fc receptor-like 3 (FCRL3) was noted in SLE-naive Treg cells, implying a potential association with microbial dysbiosis.
Is the study data available?
The sorted CD4⁺ T cell dataset and validation cohorts are available for further research.
Who supported the research?
Funding for the study was provided by multiple NIH grants and Sanofi.
| Feature | Detail |
|---|---|
| Primary finding | Study Reveals Distinct CD4⁺ T cell Subsets Linked to Systemic Lupus Erythematosus Activity and Dysfunction in Pediatric Patients |
| Method | Researchers utilized single-cell RNA sequencing of sorted blood CD4⁺ T cells. |
| Participants | Both pediatric patients and healthy donors were included in the study. |
| Data access | The sorted CD4⁺ T cell dataset and validation cohorts are available for further research. |
| Funding | Funding for the study was provided by multiple NIH grants and Sanofi. |
Deeper Dive: News & Info About This Topic
HERE Resources
Additional Resources
- PR Newswire: Lupus Foundation of America Research Showcased at 2025 American College of Rheumatology Annual Meeting
- Wikipedia: Systemic lupus erythematosus
- Medscape: Europe Adopts New Subcutaneous Route Systemic Lupus Drug
- Google Search: Systemic lupus erythematosus
- Nature: Evaluation of Targeted Therapies for Lupus
- Google Scholar: Lupus nephritis
- ScienceDirect: Regulatory T Cells in Autoimmunity
Author: STAFF HERE DALLAS WRITER
The DALLAS STAFF WRITER represents the experienced team at HEREDallas.com, your go-to source for actionable local news and information in Dallas, Dallas County, and beyond. Specializing in "news you can use," we cover essential topics like product reviews for personal and business needs, local business directories, politics, real estate trends, neighborhood insights, and state news affecting the area—with deep expertise drawn from years of dedicated reporting and strong community input, including local press releases and business updates. We deliver top reporting on high-value events such as the State Fair of Texas, Deep Ellum Arts Festival, and Dallas International Film Festival. Our coverage extends to key organizations like the Dallas Regional Chamber and United Way of Metropolitan Dallas, plus leading businesses in telecommunications, aviation, and semiconductors that power the local economy such as AT&T, Southwest Airlines, and Texas Instruments. As part of the broader HERE network, including HEREAustinTX.com, HERECollegeStation.com, HEREHouston.com, and HERESanAntonio.com, we provide comprehensive, credible insights into Texas's dynamic landscape.
