The role of inducible costimulatory molecular ligand (ICOSL) in children with neutrophilic asthma.
Background
It has been shown that certain severe and refractory asthma cases are caused by neutrophil and not eosinophil infiltration. Inducible costimulatory molecular ligand (ICOSL) expression is closely associated with tumor and autoimmune diseases, yet a limited amount of data has been published regarding the significance of ICOSL in children with neutrophilic asthma. The present study aimed to explore the clinical significance of abnormal expression of ICOSL in peripheral blood and bronchoalveolar lavage fluid (BALF) samples of children with neutrophilic asthma.


Methods
Selected children from the Children's Hospital of Soochow University who met the diagnostic criteria of asthma and excluded patients with a pathogen-positive etiology. Children who were admitted to the hospital for foreign body inhalation in the same period acted as the control group. Children with more than 50% of neutrophils in BALF samples were assigned to the neutrophilic asthma group (NA group), and the remaining subjects composed the asthma group (A group). The expression levels of ICOSL, IL-4, IL-17, IFN-γ, neutrophil elastase (NE), and matrix metalloproteinase-9 (MMP-9) were detected in plasma and BALF samples by enzyme-linked immunosorbent assays, in order to analyze the differences in the levels of cytokines and clinical characteristics between children with neutrophilic asthma and non-neutrophilic asthma. Moreover, the potential mechanism of ICOSL in neutrophilic asthma was explored.


Results
32 children were enrolled: 12 children in the NA group and 20 children in the A group. The mean hospitalization time of the NA group was longer than that of the A group (P<0.05). The concentration levels of ICOSL, IL-17, NE, and MMP-9 in plasma and BALF samples in the NA group were higher than those in the A group, while the levels of IFN-γ exhibited opposite. A significant correlation was found between ICOSL and IL-17 levels in plasma (r=0.753, P=0.012) and BALF (r=0.774, P=0.009) samples in the NA group.


Conclusions
Children with neutrophilic asthma were more severely affected, experiencing a considerably more difficult clinical treatment and longer hospitalization time. ICOSL may regulate the secretion of IL-17 by Th17 and increase the levels of NE and MMP-9, which are involved in the development of immune inflammation in neutrophils.
['Dong|Heting|H|', 'Wang|Ting|T|', 'Wang|Meijuan|M|', 'Yan|Yongdong|Y|', 'Zhang|Xinxing|X|', 'Gu|Wenjing|W|', 'Ji|Wei|W|', 'Huang|Li|L|', 'Chen|Zhengrong|Z|']
inducible costimulatory molecular ligand (ICOSL) Neutrophilic asthma cytokine