IL-33 in asthma: application note using T1/ST2 antibody
IL-33 is mainly expressed by fibroblasts, epithelial cells and endothelial cells. It is the ligand for orphan receptor, ST2. IL-33-ST2 plays a dual role, in some cases promotes Th2 cells and in other cases exacerbates Th2 and mast cell mediated inflammatory diseases. In the case of asthma, IL-33 is expressed in higher levels in both asthmatic patients and mouse models of asthma such as OVA-induced Airway inflammation. IL-33 may drive antigen sensitization and Th2-mediated inflammation during the development of asthma, where it activates dendritic cells and recruits, polarizes and activates Th2 cells. Mast cells then release TNF. IL-33 also induces eosinophilia and airway hyperresponsiveness by mast cells and IL-13.
The role of IL-33 and ST2 in asthma has been studied in multiple mouse models of airway inflammation. In this post, we highlight research from the field related to airway inflammation and the use of T1/ST2 antibodies from MD Bioproducts.
The ovalbumin-induced model of allergic airway disease (AAD) is commonly used to study many of the features observed in individuals with asthma. This model is driven by Th2 cells and is characterized by increased airway inflammation (eosinophilia), enhanced airway hyperreactivity, and increased mucus production. We have demonstrated that concomitant murine cytomegalovirus (MCMV) infection results in a decrease in airway eosinophilia in mice with AAD, which is accompanied by a decrease in Th2 cytokine production in bronchoalveolar lavage fluid (BALF) (1). We were interested in determining whether concomitant MCMV infection also altered the profile of Th2 cells in mice with AAD. As shown in Fig. 1, the percentage of Th2 cells present in the BALF decreased from 37% in AAD mice to 5% in MCMV/AAD mice, supporting the hypothesis that comcomitant MCMV infection decreases airway eosinophilia through changes in Th2 cytokines.
Figure 1. Concomitant MCMV infection decreased the percentage of Th2 cells in BALF in mice with AAD. Flow cytometric analyses of cells in BALF were gated on lymphocytes within the total CD45+ leukocyte population. The percentage of cells co-expressing CD4 and T1/ST2 was 5- to 8-fold higher in uninfected mice with AAD as compared to MCMV infected mice with AAD.
Thanks to Carol A. Wu and Lynn Puddington, Department of Immunology, University of Connecticut Health Center, Farmington, CT for sharing this data.