Involvement and repair of epithelial barrier dysfunction in allergic diseases

Abstract

The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier's role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.

Keywords: allergic diseases; barrier dysfunction; epithelial barrier; prevention and treatment; type 2 inflammation.

Figure 1

Composition of the epithelial barrier. Epithelial cells establish barriers through the intricate interplay of tight junctions (TJs), adherens junctions (AJs), and desmosomes. The TJ complex is comprised of claudins, occludins, and junctional adhesion molecules, with major cytoplasmic proteins including ZO-1, ZO-2, and ZO-3. AJs, positioned directly below the TJ, encompass E-cadherin, actin, vinculin, α-catenin, and β-catenin. Desmosomes, characterized by a symmetrical structure involving two adjacent plasma membranes, play a vital role in establishing and maintaining stable cellular junctions.

Figure 2

Epithelial barrier and type 2 immune response. When exposed to allergens, pathogenic bacteria, pollutants, etc., a compromised epithelial barrier undergoes activation, leading to the release of alarm factors by epithelial cells, including interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP). Additionally, activation may occur through the stimulation of dendritic cells, subsequently presenting antigens to Th2 cells and ILC2s cells. This activation process promotes the release of type 2 cytokines, thereby triggering and exacerbating type 2 immune responses.