Airway IL-1α promotes development of allergen-specific follicular helper T (Tfh) cells and production of IgE antibody

Abstract

Recent literature suggests that Tfh cells that produce IL-4 play a pivotal role in allergic immune responses. However, the molecular and immunological mechanisms involved in the development of Tfh cells are not fully understood. The goal of this study was to test the hypothesis that IL-1α released from alveolar macrophage plays a pivotal role in respiratory allergy. Naïve wild-type BALB/c mice and IL-4 reporter 4get mice were exposed intranasally (i.n.) to a model antigen ovalbumin (OVA) with or without serial dilutions of IL-1α. Development of allergic immune responses was analyzed by collecting mediastinal lymph nodes (mLNs) and sera, and by challenging the animals i.n. with OVA antigen. Alveolar macrophages were isolated of naïve BALB/c mice and stimulated in vitro with pollens of short ragweed or Japanese cedar. The mice exposed i.n. to OVA with IL-1α produced OVA-specific IgE antibody; the IgE response was dependent on the doses of IL-1α. These mice showed airway eosinophilia and increased lung levels of type 2 cytokines when challenged i.n. with OVA. Marked increase in the IL-4eGFP+CD4+CXCR5+ST2- Tfh cell population was observed in mLNs of mice exposed OVA plus IL-1α as compared to those mice exposed to OVA alone. Furthermore, alveolar macrophages produced and released IL-1α extracellular when they were exposed to allergen pollens in vitro. IL-1α produced by alveolar macrophages by airway allergen exposure may paly a pivotal role to promote generation of antigen-specific Tfh cells and hence development of respiratory allergy.