Eosinophils Express Functional IL-13 in Eosinophilic Inflammatory Diseases

Abstract

IL-13 is an immunoregulatory and effector cytokine in allergic diseases such as bronchial asthma. A variety of immune and non-immune cells are known as IL-13 producers. In this study we investigated whether and under what conditions human eosinophils generate IL-13. Freshly isolated highly purified peripheral blood eosinophils from patients with several eosinophilic inflammatory diseases and from normal control individuals were investigated. We observed that blood eosinophils from patients suffering from bronchial asthma, atopic dermatitis, parasitic infections, hypereosinophilic syndrome, and idiopathic eosinophilic esophagitis expressed IL-13, as assessed by ELISA, ELISPOT assay, flow cytometry, and immunocytochemistry. By using nasal polyp tissues and immunohistochemistry, we demonstrated IL-13 expression in eosinophils under in vivo conditions. In contrast, blood eosinophils from control individuals as well as blood neutrophils from both eosinophilic and control patients did not produce detectable IL-13 levels. However, when blood eosinophils from control individuals were stimulated with GM-CSF or IL-5 in vitro, they generated IL-13 mRNA and protein, suggesting that IL-13 expression by eosinophils under inflammatory conditions is a cytokine-driven process. Stimulation of blood eosinophils containing IL-13 by eotaxin resulted in a rapid release of this cytokine. Eosinophil-derived IL-13 was functional, as it increased the surface expression of the low affinity IgE receptor (CD23) on purified B cells. In conclusion, human eosinophils are able to produce and release functional IL-13 in eosinophilic inflammatory responses.

CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling

“…As shown in previous studies examining lung injury, we found that reduced eosinophils and thus remodeling mediators, including fibronectin, led to a partial reversal of ileal inflammation and remodeling. 19,25,28,29 Eosinophils are well-known sources of functional IL-13, 43 a molecule associated with remodeling and fibrosis. 44 For instance, a number of studies have highlighted the role of IL-13 as a central mediator driving the major asthmatic pathologies, including eosinophilia, mucus accumulation, fibrosis, and airway hyperresponsiveness.…”

The rise of the phoenix: the expanding role of the eosinophil in health and disease

“…Other eosinophil-derived and stored cytokines [e.g. IL-4 (23), IL-13 (24,25)] and chemokines [e.g. RANTES (26,27)] may further amplify the inflammatory milieu.…”

“…Although many of these cytokines are produced by lymphocytes, reports have demonstrated the ability of eosinophils to synthesize, store and secrete an array of cytokines [e.g. IL-4 (66, 67) and IL-13 (24,25)] and chemokines [e.g. RANTES (68)].…”

The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract

“…Blood and tissue eosinophils are terminally differentiated cells and therefore have a limited capacity to synthesize new proteins. However, based on results from multiple studies, it is now clear that eosinophils generate a wide spectrum of inflammatory and regulatory cytokines, such as TNF, TGF, GM-CSF, IL-4, IL-5, IL-8, and IL-13 (8,9). Some of these peptide mediators, such as TNF, act as amplifiers in inflammatory reactions with the risk of enhancing tissue damage.…”