Role of interleukin-23 in the development of nonallergic eosinophilic inflammation in a murine model of asthma

• Published in: Experimental & molecular medicine Vol. 52; no. 1; pp. 92 - 104
• Main Authors: Lee, Hyun Seung, Park, Da-Eun, Lee, Ji-Won, Sohn, Kyung Hee, Cho, Sang-Heon, Park, Heung-Woo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2020; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 631/250/262; 64/60; 692/699/1785/31; Allergens; Allergies; Animal models; Asthma; Autocrine signalling; Biomedical and Life Sciences; Biomedicine; CD4 antigen; Cytokines; Diesel; Epithelial cells; Epithelium; IL-1β; Inflammation; Interleukin 23; Intranasal administration; Leukocytes (eosinophilic); Lymphocytes T; Lymphoid cells; Medical Biochemistry; Medical research; Methacholine; Molecular Medicine; Polyinosinic:polycytidylic acid; Respiratory tract; Respiratory tract diseases; Stem Cells; Therapeutic applications; Thymic stromal lymphopoietin; Thymus; 생화학
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/s12276-019-0361-9

Nonallergic eosinophilic asthma (NAEA) is a clinically distinct subtype of asthma. Thus far, the pathophysiologic mechanisms underlying NAEA have not been fully elucidated. This study aimed to determine the role of IL-23 in the pathogenesis of NAEA. We developed a murine model of NAEA using recombinant IL-23 (rIL-23) plus a nonspecific airway irritant [polyinosinic-polycytidylic acid (polyI:C) or diesel exhaust particles (DEPs)] and investigated whether IL-23 plays an important role in the development of NAEA. Intranasal administration of rIL-23 (0.1 μg/mouse) plus polyI:C (0.01 μg/mouse) or DEPs (10 μg/mouse) without allergen resulted in methacholine bronchial hyperresponsiveness and eosinophilic airway inflammation in mice, which are characteristic features of NAEA. rIL-23 plus a low dose nonspecific airway irritants induced the release of innate cytokines from airway epithelium, including IL-33, thymic stromal lymphopoietin and IL-1β; these factors activated types 2 and 3 innate lymphoid cells (ILC2s and ILC3s). ILC2s and ILC3s, but not CD4+ T cells (i.e., adaptive immune cells), were important in the development of NAEA. In addition, we observed that IL-23 receptor expressions increased in airway epithelial cells, which suggests the existence of a positive autocrine loop in our murine model of NAEA. To our knowledge, this is the first report in which administration of rIL-23 plus a nonspecific airway irritant (polyI:C or DEPs) without allergen resulted in features of NAEA in mice similar to those found in humans. IL-23 may constitute a therapeutic target for NAEA in humans. Non-allergic asthma: Possible therapeutic target identified Targeting levels of a pro-inflammatory protein may help quell responses to airway irritants in patients with non-allergic asthma. Asthma often occurs when allergen exposure triggers an increase in white blood cells called eosinophils and the subsequent release of pro-inflammatory proteins such as interleukin-23 (IL-23) in the airways. However, research suggests up to one-third of sufferers have non-allergic eosinophilic asthma (NAEA), wherein airway inflammation is triggered by no specific allergen. Heung-Woo Park at the Seoul National University Medical Research Center, South Korea, and co-workers created a mouse model with excess IL-23 to examine the protein’s role in NAEA inflammation. They monitored airway responses to low doses of an acid irritant or diesel exhaust particles. The combination of high IL-23 plus an irritant triggered the release of other pro-inflammatory proteins in the airways, aggravating asthma symptoms.