Claudin-1 Mediated Tight Junction Dysfunction as a Contributor to Atopic March

Abstract

Atopic march refers to the phenomenon wherein the occurrence of asthma and food allergy tends to increase after atopic dermatitis. The mechanism underlying the progression of allergic inflammation from the skin to gastrointestinal (GI) tract and airways has still remained elusive. Impaired skin barrier was proposed as a risk factor for allergic sensitization. Claudin-1 protein forms tight junctions and is highly expressed in the epithelium of the skin, airways, and GI tract, thus, the downregulation of claudin-1 expression level caused by CLDN-1 gene polymorphism can mediate common dysregulation of epithelial barrier function in these organs, potentially leading to allergic sensitization at various sites. Importantly, in patients with atopic dermatitis, asthma, and food allergy, claudin-1 expression level was significantly downregulated in the skin, bronchial and intestinal epithelium, respectively. Knockdown of claudin-1 expression level in mouse models of atopic dermatitis and allergic asthma exacerbated allergic inflammation, proving that downregulation of claudin-1 expression level contributes to the pathogenesis of allergic diseases. Therefore, we hypothesized that the tight junction dysfunction mediated by downregulation of claudin-1 expression level contributes to atopic march. Further validation with clinical data from patients with atopic march or mouse models of atopic march is needed. If this hypothesis can be fully confirmed, impaired claudin-1 expression level may be a risk factor and likely a diagnostic marker for atopic march. Claudin-1 may serve as a valuable target to slowdown or block the progression of atopic march.

Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases

“…Patients with asthma, AD, and FA express lower levels of TJ protein claudin-1 in the skin, bronchial and intestinal epithelium. 134 AR patients have reduced expression of the transmembrane proteins occludin and claudin-7, associated with exposure to second-hand smoke and urban locations. 135 It has also been reported that a high-fat diet and antibiotics affect intestinal permeability via altering microbial composition and disrupting intestinal TJs.…”

Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier

“…When the expression level of claudin-1 is reduced, it may disrupt the normal functioning of the epithelial barrier, which may result in the development of allergies in different areas of the body. 15 Hyaluronic acid (HA), found in the epidermis, contributes to the formation of an effective barrier and the growth and specialization of keratinocytes. HA is produced by enzymes situated on the inner surface of the plasma membrane and is subsequently released as polymers directly into the extracellular matrix (ECM).…”

“…The protein Claudin‐1 (CLD‐1) is another skin structure component, that creates tight junctions and is found in high levels in the skin's epithelium. When the expression level of claudin‐1 is reduced, it may disrupt the normal functioning of the epithelial barrier, which may result in the development of allergies in different areas of the body 15 …”

“…When the expression level of claudin‐1 is reduced, it may disrupt the normal functioning of the epithelial barrier, which may result in the development of allergies in different areas of the body. 15 …”

The Role of the Microbiota in the Pathogenesis and Treatment of Atopic Dermatitis—A Literature Review

“…Filaggrin mutation is detected in up to 30% of AD patients, and it also increases the patient’s risk of developing other skin conditions, such as ichthyosis vulgaris or keratosis pilaris. Claudins, proteins crucial for forming tight junctions in the skin, airways, and GI tract epithelium, were found to be associated with the risk of allergic sensitization [ 13 , 14 ]. Polymorphisms in the CLDN-1 gene encoding claudin-1 were found to be associated with AD, and downregulation of claudin-1, claudin-4, and claudin-23 was reported in the skin of AD patients [ 14 , 15 , 16 ].…”