IL-21 was shown to potently induce Th17 differentiation and suppress FoxP3 expression 13, 14, 15, supporting the damaging effect of IL-21 on Th17 cell and Treg balance. IL-21 is produced mainly by activated CD4+ T cells but targets a much broader range of cells 12. IL-21, the most recently identified member of the type 1 cytokine family 11, was suggested to be involved in the pathogenesis of SLE. Although studies have contributed to understanding of the pathophysiology of SLE, data are lacking on cytokines and/or cellular subpopulations that could drive these T cell and B cell subset alterations and could represent potential targets for novel therapy. SLE is also associated with major alterations of blood B cell subsets 5, 6, global depletion of T regulatory cells (Treg) 7, an increase in Th lymphocytes producing interleukin 17 (Th17 cells) 8, 9, and increased expression of interferon (IFN)-inducible genes 10. T cells are needed to initiate and sustain the secretion of antibodies, in particular to histones and double-stranded DNA 4. SLE is a T and B cell-dependent autoimmune disease characterized by the appearance of a variety of autoantibodies, some of which are pathogenic 1, 3. However, longterm corticosteroids and/or immunosuppressive agents remain associated with morbidity and mortality 2. Therapeutic management is based on the type and severity of organ involvement and includes nonsteroidal antiinflammatory drugs, hydroxychloroquine, corticosteroids, and immunosuppressive agents 1. Systemic lupus erythematosus (SLE) is a disorder characterized by involvement of skin, joints, serositis, central nervous system, and kidney.

These findings suggest that IL-21, produced by distinct cellular CD4+ T cells, correlates with alterations of T cell and B cell subsets in SLE, and that targeting IL-21 could provide beneficial effects on both T cell and B cell alterations.

Tcel bcell