Dipeptidyl-peptidase IV (DPP4), originally identified as an aminopeptidase in 1960s, is an ubiquitously expressed protease presented as either a membrane-bound or soluble form. DPP4 cleaves dipeptide off from the N-terminal of its substrates, altering the bioactivity of its substrates. Subsequent studies reveal that DPP4 is also involved in various cellular processes by directly binding to a number of ligands, including adenosine deaminase, CD45, fibronectin, plasminogen, and caveolin-1. In recent years, many novel functions of DPP4, such as promoting fibrosis and mediating virus entry, have been discovered. Due to its implication in fibrotic response and immunoregulation, increasing studies are focusing on the potential role of DPP4 in inflammatory disorders. As a moonlighting protein, DPP4 possesses multiple functions in different types of cells, including both enzymatic and non-enzymatic functions. However, most of the review articles on the role of DPP4 in autoimmune disease were focused on the association between DPP4 enzymatic inhibitors and the risk of autoimmune disease. An updated comprehensive summary of DPP4’s immunoregulatory actions including both enzymatic dependent and independent functions is needed. In this article, we will review the recent advances of DPP4 in immune regulation and autoimmune rheumatic disease.
Background: It has been reported that B cell activating factor belonging to the tumor necrosis factor family (BAFF) expression is increased in chronic obstructive pulmonary disease (COPD). However its role in this chronic inflammatory disease is not fully understood. Previous studies have suggested that BAFF also affects T cell function. We therefore investigated the effects of BAFF on T lymphocytes in COPD. Methods: BAFF was detected in the cells of sputum and the plasma. Peripheral blood mononuclear cells (PBMCs) were isolated from COPD patients and treated with BAFF or BAFF plus BR3-Fc (BAFF antagonist). The apoptosis of CD4 + cells and CD8 + cells was analyzed by flow cytometry. CD4 + cells and CD8 + cells were isolated from peripheral blood of COPD patients respectively and treated with BAFF or BAFF plus BR3-Fc. Interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected in the CD4 + cells, and perforin and granzyme B were detected in the CD8 + cells. Results: BAFF expression was increased in the cells of sputum and the plasma from COPD patients compared with control subjects. The plasma BAFF levels were inversely correlated with FEV 1 percentage of predicted in patients with COPD. BAFF did not significantly alter the apoptosis of CD4 + cells, however it significantly inhibited the apoptosis of CD8 + cells from COPD patients. BAFF increased IFN-γ expression in the CD4 + cells from COPD patients, while it did not significantly alter the expresson of IL-4 in these cells. BAFF increased the expression of perforin and granzyme B in the CD8 + cells from COPD patients. Conclusions: Our findings indicate that BAFF may be involved in the inflammatory response in COPD via affecting T lymphocytes, suggesting a possible role of BAFF in the pathogenesis of COPD.
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