Abstract
IntroductionInterleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined.MethodsSerum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells.ResultsPrimary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5.ConclusionsPrimary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis.
Highlights
Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation
IL-21 alone is capable of directly inducing both B lymphocyte-induced maturation protein-1 (Blimp-1), which is required for plasma-cell differentiation, and Bcl-6, which is required for germinal center reactions [5]
The serum IL-21 levels of the patients did not correlate with anti-nuclear antibody (ANA) or rheumatoid factor (RF) titers or erythrocyte sedimentation rate (ESR), but did correlate with globulin and IgG levels
Summary
Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. The IL-21 receptor (IL-21R) consists of the IL-21R a chain and the gc chain and is expressed on T cells, NK cells, NKT cells, B cells, dendritic cells (DCs) and macrophages as well as on non-hematopoietic cells, including keratinocytes and fibroblasts [2]. IL-21 controls the functional activity of effector T helper (Th) cells and the differentiation of Th17 cells, and counteracts the suppressive effects of regulatory T cells [4]. IL-21 promotes B-cell differentiation by synergizing with BAFF and enhancing the CD40-mediated induction of activation-induced deaminase (AID) and Blimp1 [6]. Overexpression of IL-21 in mice results in hypergammaglobulinemia and autoantibody production [7]
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