The Roles of Type 2 Innate Lymphoid Cells (ILC2) in Chronic Rhinosinusitis (CRS)

Background: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases, and little is understood about its pathogenesis. Eosinophils are considered to play a major role in its pathology, but we still know little which is causing chronic immune activation and persistent eosinophilic inflammation in CRS. Recently, type 2 innate lymphoid cells (ILC2s, lineage (-), CD45 (+), CD127 (+), CD294 (+)) were identified as a candidate, which produce highly levels of Th2 cytokines such as IL-5 and IL-13, which activates eosinophils. We hypothesized that ILC2s are enriched in blood and nasal polyps in patients with eosinophilic CRS (ECRS) and are associated with its pathology.

Methods�FThe patients with CRS or pituitary adenoma (normal sinus) who underwent Endoscopic sinus surgery (ESS) in Jikei University Hospital were enrolled. We used PBMC and nasal polyps (NPs) from patients with CRS or normal subjects, and analyzed the amount of ILC2 by flow cytometry. We also investigated the distribution of ILC2s in NPs by immunohistochemistry. EDN and cytokines in NPs were measured by ELISA to investigate correlation with ILC2s. Lineage negative cells from nasal polyps were cultured in vitro with IL-33 or/and IL-2 to investigate the amount of cytokine produced by ILC2s.

Results: EDN and Th2 cytokines are significantly higher in ECRS than non-eosinophilic CRS (NECRS). EDN had strongly correlated with the numbers of ILC2s in NPs. The counts of ILC2s in NPs were significantly higher in ECRS than NECRS. Immunostained ILC2 were showed accumulated in nasal polyps of ECRS, but not in NECRS or normal subjects. ILC2’s CD25 surface expression in PBMC was significantly higher in ECRS than NECRS.  ILC2’s IL-17RB surface expression in NPs was significantly higher in NECRS than ECRS. Lineage negative cells from ECRS’ NP, but not from NECRS’, produced IL-5 and IL-13 in both IL-2 and IL-33 stimulation.

Conclusions: ILC2 are considered as candidate of the commander in ECRS, which strongly induce Th2 inflammation. There are possibility that ILC2s have several subtypes and the characteristic of ILC2s are differ from their environment.