Crocin Inhibits the Type 2 Inflammatory Response Produced by ILC2s in Eosinophilic Nasal Polyps

Abstract

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is subdivided into type 1 and type 2 inflammatory responses according to the mucosal inflammatory patterns. Crocin can reduce the level of T-helper type 2 cell (Th2) cytokines, such as interleukin-4 (IL-4), and inhibit the nuclear factor kappa-B (NF-κB) signaling pathway. Objective This study aimed to investigate the role of group 2 innate lymphoid cells (ILC2s) in type 2 inflammation in eosinophilic nasal polyps and the inhibitory effect of crocin on this inflammation. Methods Immunohistochemistry and immunofluorescence were used to detect the expression of transcription factors and the infiltration of ILC2s in tissues. An ILC2 stimulation model in vitro was constructed based on IL-33 stimulation and treated with crocin. The explant models were constructed and treated with crocin to detect the expression of type 2 inflammation-related factors. Results Significantly more GATA-binding protein-3 (GATA3)-positive cells and chemoattractant receptor-homologous molecule expressed on T-helper type 2 cell (CRTH2)-positive cells, but fewer T-box expressed in T cell (T-bet)-positive cells, were found in eosinophilic nasal polyps (NPwEos). The expression levels of GATA3 and CRTH2 were significantly higher in NPwEos. Recombinant IL-33 stimulation increased the expression of GATA3, CRTH2, and type 2 cytokines (IL-4, IL-5, and IL-13) in ILC2s. In an IL-33-stimulated in vitro ILC2 culture model, crocin inhibited the type 2 inflammatory response, especially at lower concentrations (10 µM). The explant organoids of NPwEos were constructed in vitro, and Staphylococcus aureus enterotoxin B (SEB) was used to construct the type 2 inflammation model. Crocin at 10 µM concentration inhibited type 2 inflammation induced by SEB-stimulated explants. Conclusion Crocin inhibited type 2 inflammation induced by ILC2 activation at low concentrations via inhibiting the activation of NF-κB.

“You are Always a Student, Never a Master: You Have to Keep Moving Forward” Conrad Hall

“…Alammar et al 4 performed a longitudinal case-controlled study that examined the short and long-term effects of steroids and their potential to alter the microbiome. It is also encouraging to see the in-vitro research by Xiaodong et al 5 on the inhibitory effects of Crocin (Acetaminophen) on cytokines and the signaling pathways of type 2 inflammation.…”