Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease caused by the disruption of immune tolerance. Autoantibodies against self-antigens including nuclear components are a major culprit in the induction and acceleration of systemic organ inflammation. However, the broad heterogeneity of clinical presentations has made it difficult to discover novel drug targets with high therapeutic efficacy. Long-term treatment with glucocorticoid and immunosuppressive agents could lead to catastrophic complications at late stage. Therefore, the development of a safe and novel therapy is an urgent issue. B-cell targeting agents, such as Belimumab and Rituximab are being tested in clinical trials with the aim of reducing antibody load. B-cells are an ideal target as anti-dsDNA antibodies and complements are easily monitored biomarkers of disease activity. However, B-cell targeted therapy is not sufficient for controlling autoimmunity in SLE. Given that autoantibody production is one of the representative forms of the aberrant function of the adaptive immune system against self-antigen, it is conceivable that T cells are profoundly involved in Lupus disease development and pathogenesis.
The aberration of T cells in human SLE is well documented. Examples of this include; altered intracellular signaling network and epigenetic modification, deficiency and/or overproduction of cytokines and an imbalance in the subpopulations of T cells. These phenotypic irregularities could be potential therapeutic targets. Aberrant expression of syk and abnormal histone modification in lupus T cells could be a drug target. While deficiency of IL-2 production in lupus T cells could be involved in the pathogenesis of SLE, supplementation of low-dose IL-2 targeting Treg and/or Tfh would be a potential therapeutic strategy demonstrated both in human and in murine lupus. Accumulating evidence supports the notion that modulating T cell function could also prevent the progression of autoimmune-mediated tissue damage. For instance, targeting metabolism of T cells is a promising potential for SLE treatment. Inhibiting glycolysis of dysfunctional lupus T cells has been shown to ameliorate renal pathology as well as to reduce autoantibody titers in a mouse model. Further, inhibition of glutaminolysis of T cells resulted in the reduction of pathogenic Th17 cells in lupus.
This Research Topic aims to provide an update on the role of T cells in SLE. We welcome Reviews, Mini-reviews and Original Research articles for SLE with a clinical and/or experimental viewpoint focusing on, but not limited to:
1. T cell subpopulations in SLE including Tregs, Tfh, and CTLs
2. Cytokine dysregulation in SLE
3. Metabolic regulation of dysfunctional T cells
4. Epigenetic modifications in T Cells
Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease caused by the disruption of immune tolerance. Autoantibodies against self-antigens including nuclear components are a major culprit in the induction and acceleration of systemic organ inflammation. However, the broad heterogeneity of clinical presentations has made it difficult to discover novel drug targets with high therapeutic efficacy. Long-term treatment with glucocorticoid and immunosuppressive agents could lead to catastrophic complications at late stage. Therefore, the development of a safe and novel therapy is an urgent issue. B-cell targeting agents, such as Belimumab and Rituximab are being tested in clinical trials with the aim of reducing antibody load. B-cells are an ideal target as anti-dsDNA antibodies and complements are easily monitored biomarkers of disease activity. However, B-cell targeted therapy is not sufficient for controlling autoimmunity in SLE. Given that autoantibody production is one of the representative forms of the aberrant function of the adaptive immune system against self-antigen, it is conceivable that T cells are profoundly involved in Lupus disease development and pathogenesis.
The aberration of T cells in human SLE is well documented. Examples of this include; altered intracellular signaling network and epigenetic modification, deficiency and/or overproduction of cytokines and an imbalance in the subpopulations of T cells. These phenotypic irregularities could be potential therapeutic targets. Aberrant expression of syk and abnormal histone modification in lupus T cells could be a drug target. While deficiency of IL-2 production in lupus T cells could be involved in the pathogenesis of SLE, supplementation of low-dose IL-2 targeting Treg and/or Tfh would be a potential therapeutic strategy demonstrated both in human and in murine lupus. Accumulating evidence supports the notion that modulating T cell function could also prevent the progression of autoimmune-mediated tissue damage. For instance, targeting metabolism of T cells is a promising potential for SLE treatment. Inhibiting glycolysis of dysfunctional lupus T cells has been shown to ameliorate renal pathology as well as to reduce autoantibody titers in a mouse model. Further, inhibition of glutaminolysis of T cells resulted in the reduction of pathogenic Th17 cells in lupus.
This Research Topic aims to provide an update on the role of T cells in SLE. We welcome Reviews, Mini-reviews and Original Research articles for SLE with a clinical and/or experimental viewpoint focusing on, but not limited to:
1. T cell subpopulations in SLE including Tregs, Tfh, and CTLs
2. Cytokine dysregulation in SLE
3. Metabolic regulation of dysfunctional T cells
4. Epigenetic modifications in T Cells
