Mechanistic studies on the role of CHI3L1 in eosinophilic inflammation in chronic sinusitis

Abstract

More than 10% of adults suffer from chronic rhinosinusitis (CRS), a chronic inflammatory condition that lowers quality of life, reduces productivity, and shortens work hours. Every year, more than 1 million surgeries are performed worldwide as a result of CRS. In recent years, targeted therapy for CRS has become a hotspot of research at home and abroad and has made significant progress, but CRS still has a high recurrence rate. Therefore CRS urgently needs precise targeted therapy. In the pathological process of CRS, the involvement of eosinophils is an important inflammatory mechanism. And excessive aggregation of eosinophils often leads to severe inflammatory responses. Studies have shown that chitinase 3-like protein 1 (CHI3L1) plays a key role in the activation and migration of eosinophils. This review will combine the latest research results to analyse in detail the biological properties of CHI3L1, its expression pattern in CRS, and the possible mechanisms by which it affects eosinophil aggregation by regulating immune responses and inflammatory processes, which will provide insights into the key role of CHI3L1 in the pathological process of CRS and offer a new target for the treatment of CRS.

Keywords: CHI3L1; chronic sinusitis; eosinophils; immunomodulation; inflammatory mechanisms.

Figure 1

CHI3L1’s (YKL40) biological and pathological characteristics. Cell division, apoptosis, tissue remodeling, inflammatory reactions, immunological control, vascular healing, neogenesis, and cell proliferation are some of its biological characteristics. Pathological diseases such as chronic sinusitis, inflammatory bowel disease, COPD, non-alcoholic fatty liver disease, and polymyositis have been linked to dysregulation of CHI3L1. (This protein structure is from The UniProt Knowledgebase (UniProtKB), Entry:P36222).

Figure 2

CHI3L1’s function includes oxidative damage, apoptosis, cellular pyrolysis, activation of inflammatory vesicles, development of M2 macrophages, aggregation of dendritic cells (DC), modification of the ECM (ECM), and the production of parenchymal scars.

Figure 3

CHI3L1’s function in the inflammatory response. Pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 13 (IL-13), and tumor necrosis factor-alpha (TNF-alpha) are expressed more when CHI3L1 is present. This causes a number of immune cells, including neutrophils, monocytes, and eosinophils, to become activated.Via PI3K/Akt activation, CHI3L1 influences cell adhesion, migration, and the architecture of ECM proteins like collagen, fibronectin, and proteoglycans among other things. Furthermore, via influencing endothelial cell function and angiogenic signaling pathways, CHI3L1 facilitates vascular healing and neointima development.