Circulating CXCR5+CD4+ T cells participate in the IgE accumulation in allergic asthma.

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.

From bench to bedside: Therapeutic potential of interleukin-9 in the treatment of asthma.

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.

Circulating follicular T-helper cell subset distribution in patients with asthma.

BACKGROUND: The pathogenesis of allergic asthma is primarily characterized by abnormality in the immunoglobulin E (IgE) pathway, suggesting a possible role for follicular T-helper cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR5)+CD4+ T cells, known as circulating Tfh, share common functional characteristics with Tfh cells from germinal centers. There are three subsets of circulating Tfh cells: Tfh1 (CXCR3+CC chemokine receptor [CCR] 6), Tfh2 (CXCR3CCR6) and Tfh17 (CXCR3CCR6+). However, data on circulating Tfh cell subsets distribution in patients with asthma are not available. OBJECTIVE: To investigate the circulating Tfh cell subsets distribution in patients with asthma and to assess the relationship between Tfh cell subsets distribution and the serum IgE level. METHODS: Thirty patients with severe allergic asthma and 30 age- and sex-matched healthy controls were enrolled in this study. The percentages and phenotypic assays of circulating Tfh cell subsets were assessed by flow cytometry. The total IgE levels were also measured. The correlation between the percentage of circulating Tfh cell subsets and the levels of serum total IgE was analyzed. RESULTS: Our results showed polarization of Tfh2 cells within circulating Tfh cell subsets in the patients with asthma. Phenotypic assays showed that activated Tfh2 subtypes displayed the features of Tfh cells, including invariably coexpressed programmed cell death 1 (PD-1), and inducible costimulator (ICOS). Furthermore, not only the frequency of Tfh2 cells but also the ratio (%Tfh2/%Tfh1) positively correlated with the total IgE level in the blood. CONCLUSION: Results of our data described an altered circulating Tfh subset distribution, which implied that this cell subset might play an important role in the pathogenesis of asthma.

Interleukin-27 as a potential therapeutic target for rheumatoid arthritis: has the time come?

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.