Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis

Abstract

Purpose of review Pathogenesis of nasal polyp has been largely studied based on innate and adaptive immunity of sinonasal mucosa. So far, various factors have been identified that trigger an inflammatory response in the pathogenesis of nasal polyps. In this review, we summarized recently updated information in the understanding of mechanisms in the development of chronic rhinosinusitis with nasal polyp (CRSwNP) focusing on Th2 inflammation. Recent findings Endotype of CRSwNP presented mainly Th2-skewed inflammation, and it has been associated with refractoriness and comorbidities. Staphylococcus aureus can drive Th2 inflammation by producing enterotoxins and serine protease-like protein. Moreover, S. aureus directly affected mucosal barrier function and enhanced Th2 cytokine production by fast induction of epithelial-derived innate cytokines. Epithelial-derived innate cytokines, including TSLP, IL-25, and IL-33, promote Th2 responses via the development of innate lymphoid cells. Mast cell expresses IL-5, IL-13, and periostin, and it plays a role in the pathogenesis of nasal polyps through orchestrating eosinophil infiltration. Formation of eosinophil extracellular traps and Charcot–Leyden crystals is strongly associated with disease severity and viscous mucus plug production. Therefore, it needs to be investigated mechanistically. The role of neutrophils in Th2 inflammation has been poorly understood but appears to enhance Th2 inflammation and make it more resistant to steroid therapy. Summary There is growing evidence of the role of S. aureus in innate and adaptive immunity, which contribute to Th2 inflammation in CRSwNP. Innate immunity, including epithelial-derived cytokines, plays a crucial role in the development of CRSwNP by inducing various pathways and need to be investigated more as Th2-targeted biomarkers. Recently, the role of neutrophilic inflammation in Th2 inflammation has started to be studied but still remains unclear.

Correlation of Bromodomain Protein BRD4 Expression With Epithelial–Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps

“…Nasal polyps are infiltrated with multiple inflammatory cells, such as eosinophils, neutrophils, T-helper type 2 (T H 2) cells, macrophages lymphocytes, innate lymphoid cells, and mast cells (5,6). The pathogenesis of CRSwNP that is related to T H 2-based inflammation has been shown in some published literatures (7)(8)(9). The evidence shown above demonstrates that the inflammation mainly contributes to the pathogenic process of CRSwNP.…”

Involvement of the Extracellular Matrix Proteins Periostin and Tenascin C in Nasal Polyp Remodeling by Regulating the Expression of MMPs

“…It has been known that CRSwNP patients prominently manifest eosinophilic in ammation [1] and periostin has been reported to have a role in orchestrating eosinophil in ltration. [35,36] Our data provide new insight into the role of periostin in the pathogenesis of CRSwNP, which promotes tissue remodeling via MMP production by broblasts during in ammation. Additionally, tenascin C contributes to tissue remodeling in a different manner.…”

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

“…It has been assumed that microbial agents and microbiome dysbiosis are some of the most important drivers of CRS pathogenesis. S. aureus can directly affect mucosal barrier function and drive Type 2 inflammation (Ryu and Kim, 2020). Molecular sequencing techniques are evolving in power and enable studies on total and relative microbial abundance and their functional activity within the sinonasal tract (Earl et al, 2018).…”

“…S. aureus colonization is more common in patients with CRSwNP than controls (Tomassen et al, 2016). S. aureus produces serine protease-like protein (Spl), which causes Th2-biased inflammatory responses via TSLP and IL-33 (Stentzel et al, 2017;Ryu and Kim, 2020). S. aureus specific IgE has been associated with both CRSwNP and asthma.…”

“…S. aureus specific IgE has been associated with both CRSwNP and asthma. S. aureus enterotoxins and S. aureus Spls have been found to have allergenic properties (Stentzel et al, 2017;Ryu and Kim, 2020). Type 2 cytokines inhibit t-PA (tissue plasminogen activator) resulting in the deposition of fibrin mesh to form the tissue matrix of NPs (Takabayashi et al, 2013).…”