Researchers at Weill Cornell Medicine have uncovered specific immune cell subtypes that may play a crucial role in the development of systemic lupus erythematosus (SLE) in children. This significant study, published in Nature Immunology, utilized advanced single-cell RNA sequencing to map out the CD4+ T cells from affected individuals, setting the stage for more targeted treatments that could avoid broad immunosuppression.
The investigation revealed 23 distinct CD4+ T-cell subtypes, some of which were found to be significantly expanded in children suffering from SLE. Among these, a notable subset called Th10 cells was identified, which possesses both B-cell helper and cytotoxic functions. This finding suggests that modulating the activity of Th10 cells could be a promising strategy for treating lupus patients, according to Dr. Virginia Pascual, the study’s co-senior author and the Gale and Ira Drukier Director of Children’s Health Research at Weill Cornell Medicine.
Understanding Lupus and Its Impact
Systemic lupus affects over one million individuals in the United States, with approximately 90% of patients being women of childbearing age. The disease disproportionately impacts those of Asian, African, and Native American ancestry. Symptoms frequently include inflammatory damage to vital organs such as kidneys, skin, heart, and brain, primarily driven by autoantibodies. Children diagnosed with lupus often experience more severe symptoms and a higher incidence of lupus nephritis (LN), a serious kidney condition.
Current treatment options mainly involve broad immunosuppressive therapies, which can increase the risk of infections and other complications. This new research aims to refine these approaches by pinpointing the specific CD4+ T-cell subtypes that contribute to disease pathology.
Insights into Immune Cell Subtypes
The study’s findings highlight that certain CD4+ T-cell subsets stimulate B cells to produce antibodies, with many of these T cells becoming autoreactive in lupus patients. The identification of these specific subtypes paves the way for potential targeted therapies that could maintain overall immune function while addressing the underlying causes of lupus.
The research team, led by Dr. Simone Caielli, assistant professor of immunology research in pediatrics, created an extensive map of CD4+ T-cell states. They found that the Th10 population, initially reported in a 2019 study, provides crucial help to B cells within inflamed tissues of lupus patients, underscoring their importance in autoimmune responses.
Additionally, the study revealed unexpected characteristics of regulatory CD4+ T cells (Tregs). These cells, typically responsible for suppressing immune responses, were found to be dysfunctional and excessively abundant in lupus patients, particularly those with LN. This dysfunction may be linked to microbial dysbiosis, a phenomenon previously noted in SLE patients but not yet fully understood.
The comprehensive nature of this analysis, which involved hundreds of thousands of single CD4+ T cells, offers a valuable resource for future research in lupus and immunology. Dr. Jinghua Gu, another co-senior author, emphasized that while single-cell profiling is becoming increasingly common, the necessity for large cell numbers and detailed subclustering is crucial for associating rare subpopulations with specific clinical outcomes in complex diseases like lupus.
Looking forward, the research team plans to explore whether the lupus-associated T-cell subsets identified in this study can serve as biomarkers for disease activity and as targets for future therapeutic interventions. This innovative approach has the potential to transform the landscape of lupus treatment, offering hope for more effective and less harmful therapies for patients.
For further details, see the full study: Preetha Balasubramanian et al, “Single-cell RNA profiling of blood CD4+ T cells identifies distinct helper and dysfunctional regulatory clusters in children with SLE,” Nature Immunology, March 2025. DOI: 10.1038/s41590-025-02297-2.
