Increased expression of interleukin‐7 in labial salivary glands of patients with primary Sjögren's syndrome correlates with increased inflammation

Abstract

Objective. To study the expression levels and immunostimulatory capacities of interleukin-7 (IL-7) in primary Sjögren's syndrome.Methods. Labial salivary gland (LSG) IL-7 expression was determined by immunohistochemistry, using a quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with primary Sjögren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The correlation of IL-7 expression in LSGs with parameters of local and peripheral disease was studied, and serum and salivary IL-7 levels were determined. Additionally, the effects of IL-7 on cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with primary SS were determined in vitro by Luminex multicytokine assay and compared with the effects in control subjects.Results. The expression of IL-7 in LSGs was higher in patients with primary SS compared with that in patients with non-SS sicca syndrome. IL-7 was observed primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in patients with primary SS were higher than those in control subjects. In all 30 patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters of both local and peripheral disease. Furthermore, IL-7 stimulated T cell-attracting and T cell-differentiating cytokines (monokine induced by interferon-␥ [IFN␥], IFN␥-inducible 10-kd protein,

IL-7 Abrogates Suppressive Activity of Human CD4+CD25+FOXP3+ Regulatory T Cells and Allows Expansion of Alloreactive and Autoreactive T Cells

“…However, we hypothesize that when increased IL-7 is prolonged, compromised Treg function increases the risk of expanding autoreactive T cells, or in the case of graft-versus-host disease and transplantation, alloreactive T cells. Consistent with this, IL-7 concentration is increased in the synovial fluid of patients with rheumatoid arthritis (39), the cerebrospinal fluid of patients with multiple sclerosis (10), and the salivary glands of patients with Sjögren's syndrome (40). Moreover, the major sources of IL-7 are stromal cell populations hosted in bone marrow niches (41) that house Tregs (42) and that support extensive proliferation of bone marrow resident mature T cells, including diabetogenic (43) and colitogenic (44) T cells.…”

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

“…In a mouse model for rheumatoid arthritis, anti-IL-7 treatment completely inhibited autoimmune arthritis (51). Moreover, IL-7 expression is increased in the inflamed salivary glands in primary Sjögren's syndrome compared with non-Sjögren's sicca syndrome patients (52).…”

Decreased serum level of IL-7 in patients with active Graves’ disease

“…Considering that autoimmune diseases are thought to be promoted by IL-7, these are unexpected results. Indeed, some authors have shown that IL-7 signaling could be involved in the pathogenesis of types 1 diabetes [22,23], Sjögren syndrome [24] or systemic lupus erythematosus [25] and IL-7Ra blockade could prevent or reverse these diseases. Nevertheless, our present results are confirmed by those of previous clinical studies assessing the expression of IL-7 in other autoimmune conditions.…”