IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice

Abstract

Development of persistent Th2 responses in asthma and chronic helminth infections are a major health concern. IL-10 has been identified as a critical regulator of Th2 immunity, but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated pathology, with IL-10 deficiency resulting in increased Th2-driven inflammation but also reduced airway hyperreactivity (AHR), mucus hypersecretion, and fibrosis. We demonstrate that increased IL-13 receptor α 2 (IL-13Rα2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10 -/-mice. Using models of allergic asthma and chronic helminth infection, we demonstrate that IL-10 and IL-13Rα2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13Rα2-deficient mice illustrate an indispensable role for IL-13Rα2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Rα2 are both required to control chronic Th2-driven pathological responses.

Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression

“…The absence of IL-13R␣1 or an excess of soluble IL-13R␣2 has been shown to attenuate these pathologic responses during an allergic asthma (27,34). To substantiate our findings that Th2 cytokines alter IL-31RA expression, we studied a murine model of SEA-induced allergic disease, as well as an in vivo model for Th2-driven inflammation and remodeling of the lung (20).…”

“…Animal Model of SEA-induced Allergic Asthma-Allergic asthma in animals was induced according to a previously published method (20). In brief, mice were sensitized twice (days 0 and 14) by intraperitoneal injection of 10 g of soluble egg antigen (SEA) extracted from Schistosoma mansoni parasitic eggs.…”

“…Previously, we have demonstrated that SEA acts as a potent allergen and induces Th2-cytokine-driven allergic inflammation and airway hyper-responsiveness in a mouse model of allergic asthma (20,24). To identify the effect of Type II Th2 cytokine receptors on IL-31RA expression in vivo during allergic lung disease, we studied IL-31RA expression in WT and IL-13R␣2 Ϫ/Ϫ mice exposed to SEA.…”

“…6A, mice were sensitized and challenged twice with either SEA or PBS as a control. As described previously, SEA-induced allergic disease requires no adjuvant and is sufficient to induce inflammation and hyper-responsiveness in airways (20,24). PBS-or SEA-challenged lungs were collected at 24 h after the final challenge.…”

Subclinical Interstitial Pulmonary Injury in Rheumatoid Arthritis

“…При этом повышенный уровень ИЛ-13 определяется в жидкости бронхоальвеолярного лаважа (ЖБАЛ) больных с идио-патическим легочным фиброзом (ИЛФ). Гиперэкс-прессия ИЛ-13 и его рецептора ИЛ-13Рα1 коррелиру-ет с выраженностью процесса фиброзирования легких [24][25][26]. У больных РА с субклиническим ИПЛ в на-шей работе выявлена тенденция к повышению уровня ИЛ-13.…”