Reduced Numbers of Blood Dendritic Cell Antigen 3 Positive Dendritic Cells in the Nasal Mucosa Contribute to Severe Inflammation in Patients with Allergic Rhinitis and Chronic Rhinosinusitis

Abstract

Background

Dendritic cells (DCs) are antigen-presenting cells that play a critical role in airway diseases by initiating and regulating immune responses. DCs are classified into plasmacytoid DCs (pDCs) and conventional DCs (cDCs), with the cDC lineage further divided into cDC1 and cDC2 subsets. Each subset exhibits distinct functions in immune regulation and disease pathogenesis. Thus, analyzing DC subsets is crucial for understanding the pathogenesis of airway diseases with diverse endotypes.

Objective

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS), further divided into eosinophilic CRS (ECRS) and non-eosinophilic CRS (NECRS), are typical upper airway diseases with diverse endotypes. AR and CRS often occur simultaneously, and their severity tends to increase when they are comorbid. To understand the endotypes of AR and CRS, we classified the presence or absence of AR and CRS, analyzed the changes in DC subsets in the nasal mucosa, and compared these results with clinical features.

Methods

Nasal polyp tissues and ethmoid mucosa were collected from 42 patients who underwent endoscopic sinus surgery. DC were analyzed by flow cytometry to detect the expression of blood DC antigen (BDCA)-1, BDCA-2, and BDCA-3.

Results

BDCA-3⁺ cDC levels were significantly reduced in patients with both AR and CRS, compared to those with AR alone or CRS alone. This reduction was especially prominent in patients with ECRS, polysensitization, and total serum IgE ≥ 200 IU/mL. BDCA-3⁺ cDC levels were also inversely correlated with preoperative computed tomography scores and serum eosinophil and immunoglobulin E levels.

Conclusion

BDCA-3⁺ cDC levels may be involved in mucosal immune regulation and are associated with increased disease burden in patients with comorbid AR and ECRS.

Plain Language Summary

Antigen-presenting cells called dendritic cells (DCs) are essential in conditions affecting the airways. These DC are separated into various subsets, each of which may play a special role and develop into sizable immune cell populations that regulate the etiology of illness. These various DC subsets may have distinct roles and mature into important immune cell populations that control disease pathogenesis. As a result, studying DC subsets is essential to comprehending the pathophysiology of illnesses with various endotypes. Common upper airway diseases with a variety of endotypes are allergic rhinitis (AR) and chronic rhinosinusitis (CRS), which are further subdivided into eosinophilic CRS (ECRS) and non-eosinophilic CRS (NECRS). The severity of AR and CRS tends to increase when they co-exist, and they frequently happen at the same time. We categorized the presence or absence of AR and CRS, examined alterations in DC subsets in the nasal mucosa, and contrasted these findings with clinical characteristics in order to comprehend the endotypes of AR and CRS. 42 patients who had endoscopic sinus surgery had their nasal polyp tissues and ethmoid mucosa removed. Regardless of the presence of CRS, BDCA-1⁺ cDC and BDCA-2⁺ pDC levels were similar in subjects with AR. DC were examined using flow cytometry to identify the expression of blood DC antigen (BDCA)-1, BDCA-2, and BDCA-3. In comparison to patients without CRS, BDCA-3⁺ cDC levels were considerably lower in CRS patients and even lower in ECRS patients than in NECRS patients. Patients with CRS and comorbid AR exhibited reduced BDCA-3⁺ cDC levels, which were further decreased in those who were polysensitized. The mechanisms of severe inflammation in patients with AR and ECRS may be reflected in BDCA-3⁺ cDC levels, which may be crucial for immunoregulation.