ABSTRACT
The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5+CD4+ T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5+CD4+ T cells in allergic asthmatics. Here we found the frequency of the circulating CXCR5+CD4+ T cells was raised in allergic asthma compared with healthy control (HC). Phenotypic assays showed that activated circulating CXCR5+CD4+ T cells display the key features of Tfh cells, including invariably coexpressed programmed cell death (PD)-1 and inducible costimulator (ICOS). The frequency of interleukin IL-4+-, IL-21+-producing CXCR5+CD4+ T cells was increased in allergic asthma patients compared with HC. Furthermore, sorted circulating CXCR5+CD4+ T cells from allergic asthma patients boosted IgE production in coculture assay which could be inhibited by IL-4 or IL-21 blockage. Interestingly, IL-4+-, IL-21+-CXCR5+CD4+ T cells positively correlated with total IgE in the blood. Our data indicated that circulating CXCR5+CD4+ T cells may have a significant role in facilitating IgE production in allergic asthma patients.
Subject(s)
Asthma/immunology , Germinal Center/immunology , Hypersensitivity/immunology , Immunoglobulin E/metabolism , T-Lymphocytes, Helper-Inducer/immunology , Adult , CD4 Antigens/metabolism , Cells, Cultured , Female , Flow Cytometry , Humans , Immunophenotyping , Male , Middle Aged , Receptors, CXCR5/metabolismABSTRACT
Initially identified as a T cell and mast cell growth factor, interleukin (IL)-9 has long been recognized as an important mediator of asthma. Recently, accumulating results from transgenic mice demonstrated that systemic or lung-specific overexpression of IL-9 caused asthma-associated symptoms. Moreover, anti-mIL-9 antibody (Ab) blocking treatment alleviated disease in animal models of asthma. In light of the large quantity of data from the murine models, MEDI-528, a humanized anti-IL-9 monoclonal Ab has been produced to assess the activity of IL-9 on human asthma. In order to ascertain whether it is a successful translation from bench to bedside, the biological features of IL-9 were evaluated and up-to-date information regarding the role of IL-9 in different experimental murine models and human asthma were summarized.
ABSTRACT
Interleukin (IL)-27 is a novel member of the IL-6/IL-12 family of cytokines with a broad range of pro- and anti-inflammatory properties. Recently, accumulating evidence has shown that IL-27 can play either a pathogenic or a protective role in animal models of inflammatory arthritis, depending upon the model and underlying pathogenic mechanisms. As to human system, elevated expression of IL-27 has clearly been detected in the synovial membranes and fluid from patients with rheumatoid arthritis (RA). Moreover, stimulation of IL-27 receptor with IL-27 of fibroblast-like synoviocytes from RA had a suppressive effect on the production of proinflammatory cytokines in vitro. All these findings suggest that IL-27 may have promise as a potential therapeutic target for RA. In this review, we will discuss the biological features of IL-27 and summarize recent advances on both pathogenic and protective roles of IL-27 in RA.
