Biological Properties and the Role of IL-25 in Disease Pathogenesis

Hindawi Journal of Immunology Research Volume 2018, Article ID 6519465, 8 pages https://doi.org/10.1155/2018/6519465 Review Article Biological Properties and the Role of IL-25 in Disease Pathogenesis Yuwan Liu,1 Zewei Shao,2 Guoqiang Shangguan ,2 Qingli Bie ,1 and Bin Zhang 1 2 1,2 Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, China Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, China Correspondence should be addressed to Qingli Bie; and Bin Zhang; Received 12 February 2018; Revised 18 July 2018; Accepted 16 August 2018; Published 23 September 2018 Academic Editor: Hiroshi Nakajima Copyright © 2018 Yuwan Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The interleukin- (IL-) 17 superfamily, a T cell-derived cytokine, consists of 6 ligands (IL-17A–IL-17F) and 5 receptors (IL-17RA–IL17RE). IL-17A, a prototype member of this family, is involved in the pathogenesis of allergies, autoimmune diseases, allograft transplantations, and malignancies. By contrast, IL-17B is reported to be closely related to certain diseases, particularly tumors such as breast cancer, gastric cancer, and pancreatic cancer. Recently, the biological function of IL-17E (also called IL-25) in disease, particularly airway diseases, has attracted the attention of researchers. However, studies on IL-25 are scant. In this review, we detail the structural characteristics, expression patterns, responder cells, biological properties, and role of IL-25 in disease pathogenesis. 1. Introduction Cytokines are a class of small molecular proteins with broad biological activity. They are synthesized and secreted by immune cells (monocytes, macrophages, T cells, B cells, and natural killer (NK) cells) and nonimmune cells (endothelial cells, epidermal cells, and fibroblasts). Cytokines can regulate innate and adaptive immunities, blood-cell production, cell growth, adult pluripotent stem cells (APSC), pluripotent cells, and damaged tissue repair. The interleukin- (IL-) 17 family is a recently discovered group of cytokines that share homology in amino acid sequences and have highly conserved cysteine residues [1]. The IL-17 family and its receptors, which share minimal homology with other cytokines or known proteins, have been recognized as a distinct cytokinereceptor family and are crucial for normal host immune responses; this family is associated with many human pathogeneses, including those of inflammation and cancer [2–4]. 2. Structural Characteristics of IL-25 IL-25, also named IL-17E, was first reported by Lee et al. [5] as a new member of the IL-17 family. Shortly after, Fort et al. reported that IL-25 is a cytokine produced by type 2 helper T (Th2) cells with structural similarity with IL-17 [6]. IL-25 was discovered after a BLAST search of the NCBI expression sequence tag (EST) database. A sequence of EST with a significant homology to IL-17 was discovered, and the IL-25 gene was finally cloned through reverse genetics. The IL-25 gene is located on chromosome 14 (14q11.2); it is 3987 base pairs (bp) in length and contains a 483 bp open reading frame, encoding a 161-amino acid hydrophobic signal peptide. The final products include a hydrophobic signal peptide consisting of 16 amino acids and a mature protein composed of 145 amino acids [7]. The IL-25 gene has two types of alternative splicing mRNA products that encode two subtypes (subtypes 1 and 2). The mRNA of both subtypes contains two exons; subtype 2 is less of an internal fragment than subtype 1 for a shorter N end. The mRNA of subtype 1 encodes a protein composed of 177 amino acids, and the mRNA of subtype 2 encodes a protein with 161 amino acids. Both subtypes have the same carboxy-terminal end composed of 159 amino acids. So far, no studies have reported differences in the physiological function of the two subtypes [8]. The murine IL-25 gene is located on chromosome 7, measures 985 bp in length, and encodes a protein composed of 169 amino acids. The 2 Journal of Immunology Research human and mouse IL-25 genes share 80% homology. The IL-25 proteins of the human and mouse have a potential N-glycosylation site and a conserved cysteine sequence, which is composed of 10 cysteine residues in humans and 11 cysteine residues in mice [6]. IL-25 can inhibit IL-12 production, reduce inflammation mediated by Th1, and inhibit Th17 immune responses by inducing IL-23 production [27]. 3. Expression Patterns of IL-25 Bronchial asthma is a chronic inflammatory disease of the airways, which is caused by various cells (e.g., eosinophils, mast cells, T lymphocytes, neutrophils, smooth muscle cells, and airway epithelial cells) and cellular components. The pathogenesis of asthma is related to Th2 cells, ILC2s, Th2 cytokines secreted by Th2 cells and ILC2s, and epithelial cell factors [28]; however, the pathogenesis of asthma has not yet been fully clarified. IL-25 is associated with bronchospasm after aspirin challenge, possibly via mechanisms other than altered LTC4 and PGD2 production [29]. Blockade of the IL-25 receptor (IL-25R) reduced many rhinovirus-induced exacerbation-specific responses, including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells [30, 31]. The release of IL-25 has been found to increase when the airway epithelium has been damaged, and this plays an important role in allergic diseases represented by bronchial asthma [2, 32, 33]. Similarly, Wang et al. found that IL-25 promoted the accumulation of inducible costimulator (ICOS) and T1/ST2 on nuocytes, further inducing the proinflammatory Th2 cells, and promoted Th2 cytokine responses in ovalbumin-induced airway inflammation [34]. Eosinophils are considered a typical marker of bronchial asthma airway inflammation [35]. IL-25 through immune reactivity localize with eosinophils [19]. Wong et al. suggested that IL-25 can activate eosinophils in allergic inflammation, while levels of IL-4, IL-5, eosinophil chemokines, and IgE increased [36]. The IL-25/IL-25R axis plays a crucial role in promoting the recruitment and proinflammatory function of eosinophils in allergic asthma [37]. It also plays an important role in the recruitment of eosinophils, airway mucus oversecretion, and airway remodeling in the airway of mice [2, 6, 38, 39]. Corrigan et al. found that IL-25 contributes to angiogenesis, at least partly by increasing endothelial cell VEGF/VEGF receptor expression through PI3K/Akt and Erk/MAPK pathways [40]. IL-25 can also mediate bronchial smooth muscle hyperplasia and collagen deposition around the airway [15], which further supports the idea that IL-25 promotes airway remodeling. IL-25 and its receptor IL-17RB are considered as targets f (...truncated)