FcγRIIIA Negatively Impacts Humoral Immune Responses but Not Overall Lung Inflammation in an Ovalbumin-Induced Allergic Asthma Mouse Model

Abstract

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.

Recent Advances in Experimental Allergy

“…In an ex vivo arm of the study, the expression levels of FcγRIIIA, FcγRIIB, and IgE were measured in human asthma patients. It was found that FcγRIIB negatively correlated with serum IgE; however, this was not the case for FcγRIIIA [19]. Interestingly, unlike previously published work [20-22], the work of Zhou et al [19] did not support the positive immune regulatory roles of mouse FcγRIIIA.…”

“…Zhou et al [19] investigated the role of mouse FcγRIIIA and FcγRIIB in an OVA-induced mouse asthma model. Allergic asthma was induced using OVA in wild-type, FcγRIIIA, and FcγRIIB KO mice, respectively.…”

S100A4 Is Critical for a Mouse Model of Allergic Asthma by Impacting Mast Cell Activation

“…p-Nitrophenyl phosphate solution (Southern Biotechnology Associates) was used for color development, and absorbance at 405 nm was measured by a spectrophotometer. OVA-specific IgG, IgG1, IgG2b, and IgE titers were measured as previously reported (23).…”

“…Splenocytes (2.5 × 10 5 per well) were plated into a 96-well roundbottom plate in the presence or absence of OVA (1 mg/mL) followed by culture at 37°C in 5% CO 2 for 72 hours. The Cell Counting Kit-8 (CCK-8, Dojindo Molecular Technologies) was added to each well and the cells were incubated at 37°C in 5% CO 2 for another 4 hours before being harvested for assessing the proliferative capacity of splenocytes (23). The culture supernatants were harvested for cytokine measurement.…”

Effects of caffeoylxanthiazonoside on airway inflammation in an allergic asthma mice model

“…Asthma is a chronic airway inflammatory disease with the characterizations of reversible airflow obstruction, goblet cell and smooth muscle hyperplasia, increased mucus production, hyperactivity and ultrastructural remodeling of the airways [1,2]. The prevalence of asthma in the developed countries is approximately 10 % of the population [3]. Inhaled glucocorticoids and β 2agonists are common pharmacological treatments for asthma [4].…”