Activated Human Nasal Epithelial Cells Modulate Specific Antibody Response against Bacterial or Viral Antigens

Abstract

Nasal mucosa is an immune responsive organ evidenced by eliciting both specific local secretory IgA and systemic IgG antibody responses with intra-nasal administration of antigens. Nevertheless, the role of nasal epithelial cells in modulating such responses is unclear. Human nasal epithelial cells (hNECs) obtained from sinus mucosa of patients with chronic rhinosinusitis were cultured in vitro and firstly were stimulated by Lactococcus lactis bacterium-like particles (BLPs) in order to examine their role on antibody production. Secondly, both antigens of immunodominant protein IDG60 from oral Streptococcus mutans and hemagglutinin (HA) from influenza virus were tested to evaluate the specific antibody response. Stimulated hNECs by BLPs exhibited a significant increase in the production of interleukin-6 (IL-6), and thymic stromal lymphopoietin (TSLP). Conditioned medium of stimulated hNECs has effects on enhancing the proliferation of CD4+ T cells together with interferon-γ and IL-5 production, increasing the costimulatory molecules on dendritic cells and augmenting the production of IDG60 specific IgA, HA specific IgG, IgA by human peripheral blood lymphocytes. Such production of antigen specific IgG and IgA is significantly counteracted in the presence of IL-6 and TSLP neutralizing antibodies. In conclusion, properly stimulated hNECs may impart immuno-modulatory effects on the antigen-specific antibody response at least through the production of IL-6 and TSLP.

Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation

“…Furthermore, TSLP expression was reduced in the cells overexpressing caveolin-1, indicating a functional crosstalk between epithelial cell-cell adhesion and induction of airway inflammation [8]. Besides the triggers mentioned above, TSLP stimulation via peptidoglycan matrix of bacterial lactococcus bacteria like particles (BLP) has also been reported [9]. These findings suggest that regulators for TSLP release are more diverse than previously anticipated and that multiple pathways may be involved in pathogenesis of allergic diseases.…”

Frontline Science: Nasal epithelial GM-CSF contributes to TLR5-mediated modulation of airway dendritic cells and subsequent IgA response

“…For an in vitro blockage experiment, conditioned medium from mNECs stimulated by FliC was preincubated with neutralizing antibodies, including GM-CSF (clone MP1-22E9; BioLegend), IL-6 (clone MP5-20F3; BioLegend), TSLP (clone 152614; R&D Systems, Minneapolis, MN, USA), control IgG1 (clone RTK2071; BioLegend), or control IgG2a (clone RTK2758; BioLegend), for 30 min at 37°C. Amounts of 20 mg/ml anti-GM-CSF, 2 mg/ml anti-IL-6 and 4 mg/ml anti-TSLP were used [14,28,29]. Following stimulation, these DCs were harvested for detection or washed 3 times for further experiments.…”

Upper Airway Stem Cells: Understanding the Nose and Role for Future Cell Therapy

“…There was increased CP110 expression in rhinosinal mucosa from patients with CRS which might contribute to the poor ciliation observed in patients with CRS [40]. Properly stimulated hNECs may impart immuno-modulatory effects on the antigen-specific antibody response at least through the production of IL-6 and thymic stromal lymphopoietin (TSLP) [46]. It has been demonstrated recently that reconstituted epithelia from human NP epithelial cells cultured in ALI system provide a 3D in vitro model that could be useful both for studying the role of epithelium in CRSwNP while developing new therapeutic strategies, including cell therapy, for CRSwNP [47•].…”