Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P<0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r=0.15, P<0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

Plasma exudation and vasodilatation are key microvascular features of acute inflammation. Exudation and vasodilatation responses in the weal area after skin prick testing with histamine are essentially completed within 30 min. There is evidence to suggest that vasodilatation lasts considerably longer after provocation with allergen, but there is no information on the duration of plasma exudation. The purpose of this study was to measure the time course of the microvascular inflammatory response in the skin after histamine and allergen provocation. Skin prick tests were performed with histamine, allergen (ovalbumin) or saline (control) on guinea-pigs which were shaved on their backs. Radioactive 113mIn was used to label transferrin as a plasma tracer. Radioactivity was recorded from the superficial part of the skin by external detection of conversion electrons from the decay of 113mIn. The increase in count rate, corresponding to tracer accumulation by vasodilatation and/or plasma exudation, was used as a measure of the microvascular inflammatory response to skin prick test. The microvascular response was studied immediately and up to 30 min after provocation. The largest response to histamine and allergen occurred immediately after provocation. The exudative response then gradually declined to be absent after 25-30 min. Skin prick test with saline resulted in a small response of shorter duration. We conclude that the microvascular reaction to histamine as well as allergen provocation in guinea-pig skin has a rapid onset and a duration of approximately 30 min.

Background: Fcγ receptors (FcγR) play substantial immune regulatory roles both positively and negatively in pathophysiological processes including allergy and asthma. Compared with FcγRIIB which is classically defined as an inhibitory receptor, mouse FcγRIIIA and its functional human homologue FcγRIIA have been assumed to be activating receptors. However, evidence demonstrating inhibitory regulation by mouse FcγRIIIA has recently been emerging. Objective: To dissect the contributory roles of mouse FcγRIIIA (human FcγRIIA) in parallel with FcγRIIB in an ovalbumin (OVA)-induced mouse model of asthma and to preliminarily assess the correlation of the respective FcγR with circulating IgE levels in human asthma patients. Methods: Wild-type, FcγRIIB^–/–, and FcγRIIIA^–/– mice were used in an OVA-induced asthma model followed by assessment of the allergic pathology focused on the lung tissues. Expression levels of FcγRIIB, FcγRIIA, and FcγRIIIA on peripheral blood mononuclear cells (PBMC) together with the circulating IgE levels in the serum from patients with allergic asthma were analysed. Results: Although enhanced humoral immune responses typically represented by augmented OVA-specific IgG and IgE levels in serum were observed in the absence of FcγRIIIA in the mouse asthma model, no overall regulation by FcγRIIIA, especially in terms of those parameters measuring lung tissue inflammation, was recorded. As expected, in the absence of FcγRIIB, augmented immune responses measured as serum antibody levels as well as those in various regulatory pathways in this mouse asthma model were observed. The expression levels of human FcγRIIB but not FcγRIIA were negatively correlated with serum levels of IgE in human asthma patients. Conclusion: We did not find major evidence demonstrating an immune inhibitory role of mouse FcγRIIIA in this OVA-induced mouse asthma model. As asthma is a complex disease and the immune regulatory responses involve sophisticated components and pathways, the exact roles of FcγRIIIA as well as its human functional homologue FcγRIIA in asthma still await further clarification using other mouse asthma models as well as clinical studies.

BackgroundThe calcium-binding protein S100A4 demonstrates important regulatory roles in many biological processes including tumorigenesis and inflammatory disorders such as allergy. However, the specific mechanism of the contribution of S100A4 to allergic diseases awaits further clarification.ObjectiveTo address the effect of S100A4 on the regulation of mast cell activation and its impact on allergy.MethodsBone marrow-derived cultured mast cells (BMMCs) were derived from wild-type (WT) or S100A4-/- mice for in vitro investigation. WT and S100A4-/- mice were induced to develop a passive cutaneous anaphylaxis (PCA) model, a passive systemic anaphylaxis (PSA) model, and an ovalbumin (OVA)-mediated mouse asthma model.ResultsFollowing OVA/alum-based sensitization and provocation, S100A4-/- mice demonstrated overall suppressed levels of serum anti-OVA IgE and IgG antibodies and proinflammatory cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung exudates. S100A4-/- mice exhibited less severe asthma signs which included inflammatory cell infiltration in the lung tissue and BALF, and suppressed mast cell recruitment in the lungs. Reduced levels of antigen reencounter-induced splenocyte proliferation in vitro were recorded in splenocytes from OVA-sensitized and challenged mice that lacked S100A4-/-. Furthermore, deficiency in the S100A4 gene could dampen mast cell activation both in vitro and in vivo, evidenced by reduced β-hexosaminidase release and compromised PCA and PSA reaction. We also provided evidence supporting the expression of S100A4 by mast cells.ConclusionS100A4 is required for mast cell functional activation, and S100A4 may participate in the regulation of allergic responses at least partly through regulating the activation of mast cells.