The Role of Tight Junctions in Atopic Dermatitis: A Systematic Review

Abstract

Background: Tight junctions are transmembrane proteins that regulate the permeability of water, solutes including ions, and water-soluble molecules. The objective of this systematic review is to focus on the current knowledge regarding the role of tight junctions in atopic dermatitis and the possible impact on their therapeutic potential. Methods: A literature search was performed in PubMed, Google Scholar, and Cochrane library between 2009 and 2022. After evaluation of the literature and taking into consideration their content, 55 articles were finally included. Results: TJs’ role in atopic dermatitis extends from a microscopic scale to having macroscopic effects, such as increased susceptibility to pathogens and infections and worsening of atopic dermatitis features. Impaired TJ barrier function and skin permeability in AD lesions is correlated with cldn-1 levels. Th2 inflammation inhibits the expression of cldn-1 and cldn-23. Scratching has also been reported to decrease cldn-1 expression. Dysfunctional TJs’ interaction with Langerhans cells could increase allergen penetration. Susceptibility to cutaneous infections in AD patients could also be affected by TJ cohesion. Conclusions: Dysfunction of TJs and their components, especially claudins, have a significant role in the pathogenesis and vicious circle of inflammation in AD. Discovering more basic science data regarding TJ functionality may be the key for the use of specific/targeted therapies in order to improve epidermal barrier function in AD.

Polymeric Nanoparticles’ Accumulation in Atopic Dermatitis: Clinical Comparison between Healthy, Non-Lesional, and Lesional Skin

“…The degree of downregulation of Claudin-1 in AD lesion skin was correlated to the dermal infiltration intensity, suggesting that the decreased mRNA expression of Claudin-1 is triggered by skin inflammation [24]. Claudin-1's downregulation also correlated with the Th-2 inflammation pathway and was also aggravated by scratching of the skin [25]. Regarding Claudin-4, we observed decreased immune intensity in non-lesional skin compared to the healthy controls, while lesional skin has shown a similar intensity to healthy skin.…”

“…The degree of downregulation of Claudin-1 in AD lesion skin was correlated to the dermal infiltration intensity, suggesting that the decreased mRNA expression of Claudin-1 is triggered by skin inflammation [ 24 ]. Claudin-1’s downregulation also correlated with the Th-2 inflammation pathway and was also aggravated by scratching of the skin [ 25 ].…”

The Potential of Campanula takesimana Callus Extract to Enhance Skin Barrier Function

“…Furthermore, tight junction proteins expressed in the stratum granulosum are another core component in the formation of the epidermal barrier. Tight junctions and the stratum corneum have a synergistic effect on the formation of a strong skin barrier, and reduced expression of tight junction proteins and decreased skin barrier function have been well reported in AD [27,28]. Thus, restoring skin barrier-related proteins is important in controlling the disease activity of AD.…”

Are Antimicrobial Peptides a 21st-Century Solution for Atopic Dermatitis?

“…These are structures that have a connection role between cells, exist in every human epithelium, and have various roles depending on the tissue they are located in (e.g., homeostasis control in the central nervous system or impeding the penetration of pathogens in the intestine) [22,23]. In healthy skin, TJs are part of the mechanism for managing cellular differentiation, proliferation and cascading processes involved in maintaining and managing skin homeostasis and permeability [24,25]. On the other hand, in AD patients, TJs are normally dysfunctional and contribute to the irregular barrier function of the skin.…”