Epithelium, inflammation, and immunity in the upper airways of humans: studies in chronic rhinosinusitis

Abstract

The purpose of this review is to discuss recent findings made during studies of the upper airways and sinuses of people with chronic rhinosinusitis (CRS) in the context of the literature. CRS is a chronic inflammatory disorder affecting nearly 30 million Americans and is generally resistant to therapy with antibiotics and glucocorticoids (Meltzer EO and coworkers, J Allergy Clin Immunol 2004;114:155-212). We have formed a collaboration that consists of otolaryngologists, allergists, and basic scientists to address the underlying immunologic and inflammatory processes that are occurring in, and possibly responsible for, this disease. The main emphasis of our work has been to focus on the roles that epithelium, in the sinuses and upper airways, plays as both a mediator and regulator of immune and inflammatory responses. It is not our intention here to provide a comprehensive review of the literature in this area, but we will try to put our work in the context of the findings of others (Kato A and Schleimer RP, Curr Opin Immunol 2007;19:711-720; Schleimer RP and coworkers, J Allergy Clin Immunol 2007;120:1279-1284). In particular, we discuss the evidence that epithelial cell responses are altered in CRS, including those relevant to regulation of dendritic cells, T cells, B cells, and barrier function.

Figure 1.

(A) T cells in chronic rhinosinusitis (CRS). (B) BAFF staining in CRS with nasal polyp (CRSwNP). (C) BAFF in nasal polyp tissue. (D) SPINK5 in sinus mucosa.

Figure 2.

Hypothesis regarding the role that local cytokine responses play in the recruitment and activation of B lymphocytes in CRS. (1) Activation of epithelium with Toll-like receptor (TLR) agonist (especially TLR3) leads to BAFF production via an autocrine stimulation pathway that involves IFN-β. (2) BAFF is released by epithelial cells as well as hematopoietic lineage cells in CRSwNP. (3) B cells are stimulated to undergo proliferation, class switch recombination, differentiation, and survival by BAFF and other local factors, leading to production of IgA, IgE, and other immunoglobulin isotypes. (4) The processes of local B cell activation and IgA production as well as IgA transport are regulated by the 12/15 lipoxygenase pathway. See text for details.