Research conducted by investigators at Weill Cornell Medicine has identified distinct immune cell subtypes that contribute to the development of systemic lupus erythematosus (SLE). This study, published in Nature Immunology in March 2025, utilized single-cell RNA sequencing to analyze CD4+ T cells from children diagnosed with SLE, uncovering potential pathways for more targeted therapies.
The research team mapped the CD4+ T-cell profiles of children with lupus alongside healthy controls. This detailed analysis revealed a complex landscape of immune cell subtypes, highlighting the diversity and specific roles of CD4+ T cells in the pathogenesis of lupus, a chronic autoimmune disease that affects over one million individuals in the United States, predominantly women of childbearing age.
Findings on CD4+ T Cell Subtypes
Historically, CD4+ T cells have been linked to the immune response in lupus, but their full range of subtypes and functions had not been thoroughly characterized. The research identified a total of 23 unique CD4+ T-cell subtypes, some of which were significantly expanded in patients with lupus and lupus nephritis (LN). Notably, the study highlighted a subset known as Th10 cells. These cells possess both B-cell helper and cytotoxic characteristics, providing additional insight into their role in autoimmune responses.
Dr. Virginia Pascual, co-senior author and the Ronay Menschel Professor of Pediatrics at Weill Cornell Medicine, emphasized the potential of targeting Th10 cells in therapeutic strategies. “Modulation of a particular CD4+ T-cell subset called Th10 might be a good strategy for treating patients with lupus,” she stated. The exploration of this subset could lead to treatments that do not rely on broad immunosuppression, which often increases the risk of infections.
The Role of Regulatory T Cells
The study also examined regulatory CD4+ T cells (Tregs), typically known for their role in suppressing immune responses. Surprisingly, Tregs were found to be dysfunctional and in increased numbers among lupus patients. This dysfunction, particularly pronounced in those with lupus nephritis, may contribute to the disease’s severity. Dr. Simone Caielli, another co-senior author and assistant professor of immunology research in pediatrics at Weill Cornell Medicine, noted the potential link between Treg dysfunction and microbial dysbiosis, a condition previously reported but not well understood in lupus patients.
The implications of these findings extend beyond understanding the disease’s mechanisms; they offer a new resource for future lupus research. By analyzing hundreds of thousands of single CD4+ T cells, the team created a comprehensive map that can facilitate the identification of disease-associated cell subpopulations.
Dr. Jinghua Gu, also a co-senior author and assistant professor of research in pediatrics at Weill Cornell Medicine, stated, “Single-cell profiling is now very widespread, but a new lesson we learned here is that you may need very large numbers of cells combined with deep subclustering to associate a rare subpopulation with specific clinical manifestations, especially in a disease as heterogeneous as lupus.”
The research team is currently investigating whether these identified T-cell subsets could serve as biomarkers for disease activity and targets for future therapeutic interventions, marking a significant step forward in the quest for more effective lupus treatments.
