Association Between Circulating Levels of the Novel TNF Family Members APRIL and BAFF and Lymphoid Organization in Primary Sjögren’s Syndrome

Jonsson, Malin V.; Szodoray, Péter; Jellestad, Stig; Jönsson, Roland; Skarstein, Kathrine

doi:10.1007/s10875-005-4091-5

Cited by 200 publications

(168 citation statements)

References 37 publications

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“…Interestingly, BAFF was found to be significantly up-regulated in pSjS monocytes on the mRNA level (data not shown). BAFF plays a role in the survival of (autoreactive) B cells and promotes CD40-independent class switch recombination, and has indeed been found to be increased both systemically and in the salivary glands of pSjS patients [35][36][37][38]. Interestingly, expression of CD40 by pDC was significantly higher in pSjS patients positive for anti-SS-B antibodies (data not shown).…”

Section: Discussionmentioning

confidence: 86%

Systemic increase in type I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cells

et al. 2008

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In the salivary glands of primary Sjögren's syndrome (pSjS) patients, type I IFN activity is increased, but systemic levels of type I IFN proteins are rarely detected. This study focused on the systemic activity of type I IFN in pSjS, as well as the role of peripheral plasmacytoid dendritic cells (pDC). Monocytes obtained from pSjS patients showed an increased expression of 40 genes. Twenty-three of these genes (58%), including IFI27, IFITM1, IFIT3 and IFI44, were inducible by type I IFN. pSjS serum had an enhanced capability of inducing IFI27, IFITM1, IFIT3 and IFI44 in the monocytic cell line THP-1, likely due to the action of IFN-b. This effect could be inhibited by blocking the type I IFN receptor, supporting a high type I IFN bioactivity in pSjS serum. In addition, circulatory pDC showed increased expression of CD40. This expression was correlated to the expression level of the type I IFN-regulated genes IFI27 and IFITM1 in monocytes of the same individual. This study indicates that the increased type I IFN activity observed in pSjS patients is not only a local but also a systemic phenomenon and points to pDC as a possible source of this activity.

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Section: Discussionmentioning

confidence: 86%

Systemic increase in type I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cells

et al. 2008

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“…Human TSLPsecreting tonsillar epithelial cells produce BAFF to induce class switching by stimulating B cells (48). In addition, a recent human study suggested an association between circulating levels of BAFF in ectopic germinal centers of the salivary gland in primary Sjögren's syndrome (16,37). Taken together, these results suggest that TSLP, together with BAFF, produced by H. pylori-infected gastric mucosa leads to inflammatory Th2 responses and maintenance of B-cell activation.…”

Section: Discussionmentioning

confidence: 87%

Helicobacter pylori Promotes the Production of Thymic Stromal Lymphopoietin by Gastric Epithelial Cells and Induces Dendritic Cell-Mediated Inflammatory Th2 Responses

et al. 2010

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Helicobacter pylori colonizes the stomach and induces strong, specific local and systemic humoral and cell-mediated immunity, resulting in the development of chronic gastritis in humans. Although H. pyloriinduced chronic atrophic gastritis is characterized by marked infiltration of T helper type 1 (Th1) cytokineproducing CD4؉ T cells, almost all of the inflamed gastric mucosae also contain focal lymphoid aggregates with germinal centers. In addition, typical H. pylori-induced chronic gastritis in children, called follicular gastritis, is characterized by B-cell follicle formation in the gastric mucosa. The aim of this study was to examine whether thymic stromal lymphopoietin (TSLP), an epithelial-cell-derived cytokine inducing a dendritic cell (DC)-mediated inflammatory Th2 response, is involved in Th2 responses triggering B-cell activation in H. pylori-induced gastritis. Here, we show that H. pylori triggered human gastric epithelial cells to produce TSLP, together with the DC-attracting chemokine MIP-3␣ and the B-cell-activating factor BAFF. After DCs were incubated with supernatants from H. pylori-infected epithelial cells, the conditioned cells expressed high levels of costimulatory molecules, such as CD80, and triggered naïve CD4؉ T cells to produce high levels of the Th2 cytokines interleukin-4 and interleukin-13 and of the inflammatory cytokines tumor necrosis factor alpha and gamma interferon. In contrast, after incubation of the supernatants with the neutralizing antibodies to TSLP, the conditioned DCs did not prime T cells to produce high levels of Th2 cytokines. These results, together with the finding that TSLP was expressed by the epithelial cells of human follicular gastritis, suggest that H. pylori can directly trigger epithelial cells to produce TSLP. It also suggests that TSLP-mediated DC activation may be involved in Th2 responses triggering B-cell activation in H. pylori-induced gastritis.Helicobacter pylori (H. pylori) infection in the stomach induces chronic gastritis associated with the development of peptic ulcer diseases, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma in humans (3,8,35). Although H. pylori-induced chronic atrophic gastritis is characterized by marked infiltration of T helper type 1 (Th1) cytokine-producing CD4 ϩ T cells (3,8,35), almost all of the inflamed gastric mucosae also contain focal lymphoid aggregates with germinal centers (5, 11). In addition, typical H. pylori-induced chronic gastritis in children, called follicular gastritis, is characterized by B-cell follicle formation in the gastric mucosa (10,11,34). Th2 responses triggering B-cell activation appear to be involved in the development of lymphoid aggregates with germinal centers. However, molecular mechanisms to induce Th2 responses triggering B-cell activation are not clear.In humans, an epithelial-cell-derived cytokine, thymic stromal lymphopoietin (TSLP), activates CD11c ϩ myeloid dendritic cells (DCs), and activated DCs strongly upregulate the expression of costimulatory mo...

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“…In the investigation of both serum BAFF and APRIL, in a comparison with six healthy donors the serum levels of both BAFF and APRIL in 29 SjS patients were elevated, but compared with SjS patients without anti-SSA antibody, only the serum APRIL levels in the SjS patients with anti-SSA antibody were elevated [88].…”

Section: Sjögren's Syndromementioning

confidence: 97%

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

Hirayama¹,

Nagai²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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The tumor necrosis factor superfamily (TNFSF) member and cytokine known as B-cell activation factor belonging to the TNF-family (BAFF) has been identified as one of the key factors in the selection and survival of B cells. Overexpression of BAFF in mice leads to autoimmunity, whereas BAFF-deficient mice lack mature B cells. Although under normal concentrations of BAFF, non-self-reactive B cells survived and autoreactive B cells were deleted, a higher concentration of BAFF contributed to the survival of autoreactive B cells and elevated autoantibody production. Lupus-prone mice have increased serum levels of BAFF during the onset and progression of disease. The serum BAFF levels are elevated in patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ANCA-associated vasculitis, and showed positive correlations with autoantibodies.

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Association Between Circulating Levels of the Novel TNF Family Members APRIL and BAFF and Lymphoid Organization in Primary Sjögren’s Syndrome

Cited by 200 publications

References 37 publications

Systemic increase in type I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cells

Systemic increase in type I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cells

Helicobacter pylori Promotes the Production of Thymic Stromal Lymphopoietin by Gastric Epithelial Cells and Induces Dendritic Cell-Mediated Inflammatory Th2 Responses

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

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