2026-05-08
Immune cells and systemic lupus: a global dysregulation of the immune system
Allergology and Immunology Rhumatology
By Ana Espino | Published on May 8, 2026 | 4 min read
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by profound dysregulation of immune homeostasis, involving both innate and adaptive immunity. Recent advances, particularly through single-cell RNA sequencing and multi-omics approaches, have made it possible to identify specific alterations in cellular subpopulations, paving the way for more personalized medicine.
Lupus is driven by a major immune imbalance combining abnormal activation of immune cells, excessive production of cytokines and autoantibodies, and hyperactivation of the type I interferon pathway. This imbalance between innate and adaptive immunity forms the basis of its pathophysiology, relying on a complex and dynamic network of interactions in which all immune cells contribute to the initiation and maintenance of the autoimmune response.
B cells are at the core of lupus. Their hyperactivation leads to increased production of autoantibodies and differentiation into pathogenic plasma cells. At the same time, the regulatory functions of B regulatory cells are impaired, contributing to the loss of immune tolerance. These features explain why B cells are a major therapeutic target, particularly through anti-CD20 or anti-BAFF therapies.
CD4+ T cells play a central role in orchestrating the immune response. In lupus, there is an increase in pro-inflammatory subpopulations, including T follicular helper cells, Th1, and Th17 cells, which drive inflammation and activate B cells. Conversely, regulatory T cells are reduced or dysfunctional, promoting loss of tolerance and persistent immune activation.
Dendritic cells play a key role in initiating the autoimmune response. They present autoantigens to lymphocytes and produce large amounts of type I interferon, particularly plasmacytoid dendritic cells. Certain subpopulations, such as DC3, exhibit a pro-inflammatory profile closely associated with disease activity, amplifying the immune response.
Innate immunity actively contributes to sustaining inflammation. Neutrophils and monocytes produce extracellular structures—NETs and METs—that release autoantigens and stimulate the immune system. Macrophages display an imbalance between pro-inflammatory and regulatory phenotypes, contributing both to chronic inflammation and tissue damage. Together, these mechanisms maintain a self-perpetuating inflammatory loop.
Natural killer (NK) cells show functional impairment, characterized by reduced cytotoxic activity and defective clearance of apoptotic cells. This failure promotes the accumulation of cellular debris, which becomes a source of autoantigens and contributes to the activation of the autoimmune response.
Lupus is driven by a self-sustaining pathological cycle. It begins with defective clearance of apoptotic cells, followed by the release of autoantigens. These activate dendritic cells, leading to type I interferon production. This activation then stimulates T and B lymphocytes, resulting in the production of autoantibodies and the formation of immune complexes, which drive chronic inflammation. Therapeutic implications New therapeutic strategies aim to specifically target the cells and pathways involved in the disease. These include treatments directed against B cells, T–B cell interactions, and the interferon pathway. Innovative approaches, such as anti-CD19 CAR T cells, illustrate this shift toward targeted therapies. The goal is now to develop precision medicine based on each patient’s immunological profile.
Lupus is not the result of a defect in a single cell type, but rather a systemic disease involving the entire immune network. It arises from complex interactions between B and T lymphocytes, dendritic cells, and innate immunity. This integrated view now allows for a better understanding of disease flares, the identification of biomarkers, and the development of targeted therapies. The future lies in a personalized approach, guided by the cellular and molecular signatures unique to each patient.
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by profound dysregulation of immune homeostasis, involving both innate and adaptive immunity. Recent advances, particularly through single-cell RNA sequencing and multi-omics approaches, have made it possible to identify specific alterations in cellular subpopulations, paving the way for more personalized medicine.
A central immune imbalance
Lupus is driven by a major immune imbalance combining abnormal activation of immune cells, excessive production of cytokines and autoantibodies, and hyperactivation of the type I interferon pathway. This imbalance between innate and adaptive immunity forms the basis of its pathophysiology, relying on a complex and dynamic network of interactions in which all immune cells contribute to the initiation and maintenance of the autoimmune response.
Key role of different immune cells
1. B lymphocytes: central players
B cells are at the core of lupus. Their hyperactivation leads to increased production of autoantibodies and differentiation into pathogenic plasma cells. At the same time, the regulatory functions of B regulatory cells are impaired, contributing to the loss of immune tolerance. These features explain why B cells are a major therapeutic target, particularly through anti-CD20 or anti-BAFF therapies.
2. T lymphocytes: imbalance of subpopulations
CD4+ T cells play a central role in orchestrating the immune response. In lupus, there is an increase in pro-inflammatory subpopulations, including T follicular helper cells, Th1, and Th17 cells, which drive inflammation and activate B cells. Conversely, regulatory T cells are reduced or dysfunctional, promoting loss of tolerance and persistent immune activation.
3. Dendritic cells (DCs): triggers of autoimmunity
Dendritic cells play a key role in initiating the autoimmune response. They present autoantigens to lymphocytes and produce large amounts of type I interferon, particularly plasmacytoid dendritic cells. Certain subpopulations, such as DC3, exhibit a pro-inflammatory profile closely associated with disease activity, amplifying the immune response.
4. Innate immunity: amplification of inflammation
Innate immunity actively contributes to sustaining inflammation. Neutrophils and monocytes produce extracellular structures—NETs and METs—that release autoantigens and stimulate the immune system. Macrophages display an imbalance between pro-inflammatory and regulatory phenotypes, contributing both to chronic inflammation and tissue damage. Together, these mechanisms maintain a self-perpetuating inflammatory loop.
5. NK cells: dysfunction and impaired clearance
Natural killer (NK) cells show functional impairment, characterized by reduced cytotoxic activity and defective clearance of apoptotic cells. This failure promotes the accumulation of cellular debris, which becomes a source of autoantigens and contributes to the activation of the autoimmune response.
A key mechanism: the autoimmune loop
Lupus is driven by a self-sustaining pathological cycle. It begins with defective clearance of apoptotic cells, followed by the release of autoantigens. These activate dendritic cells, leading to type I interferon production. This activation then stimulates T and B lymphocytes, resulting in the production of autoantibodies and the formation of immune complexes, which drive chronic inflammation. Therapeutic implications New therapeutic strategies aim to specifically target the cells and pathways involved in the disease. These include treatments directed against B cells, T–B cell interactions, and the interferon pathway. Innovative approaches, such as anti-CD19 CAR T cells, illustrate this shift toward targeted therapies. The goal is now to develop precision medicine based on each patient’s immunological profile.
Conclusion
Lupus is not the result of a defect in a single cell type, but rather a systemic disease involving the entire immune network. It arises from complex interactions between B and T lymphocytes, dendritic cells, and innate immunity. This integrated view now allows for a better understanding of disease flares, the identification of biomarkers, and the development of targeted therapies. The future lies in a personalized approach, guided by the cellular and molecular signatures unique to each patient.
Read next : Efficacy and safety of biotherapies in the treatment of systemic lupus erythematosus
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions
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