Tight Junction’s role in atopic dermatitis
Abstract
The pathophysiology of atopic dermatitis (AD) is complex and multifactorial, primarily involving barrier dysfunction. Tight junctions (TJs) are intercellular junctions that are important for establishing the epithelial barrier and maintaining its polarity. Tight junctions have an essential role in the development and function of the stratum corneum, indicating that diseases with TJ dysfunction will cause a disruption on the stratum corneum homeostasis. Atopic dermatitis is a skin disorder that affects 20% of the human population. The complex interactions between damaged skin barrier, skin inflammation, and itching contribute to the development, progression, and duration of AD. Elevated epicutaneous sensitization and skin sensitivity to exogenous stimuli are both caused by skin barrier dysfunction. Desmosomes and TJs hold a complex matrix of structural proteins and lipids that make up the skin barrier together. These aspects form the foundation of barrier disruption in AD. The discovery of the TJ protein Claudin-1 plays a key role in human epidermal tissue and keratinocyte proliferation. Barrier disruption in patients with AD is not only confined to the stratum corneum but also to the TJs, and regulation of these barriers may provide opportunities for new therapies in people with AD or other atopic diseases.References
Anggraeni S, Umborowati MA, Damayanti, Endaryanto A, Rosita Sigit Prakoeswa C. Correlation between Skin Prick Test and Specific IgE of Local Mites Allergen in Atopic Dermatitis Patients: an Indonesian Study. CMUJ Nat Sci. 2022; 2020;21(4):e2022053.
Nutten S. Atopic dermatitis: Global epidemiology and risk factors. Ann Nutr Metab. 2015;66:8–16.
Sihaloho K, Indramaya DM. Retrospective Study: Atopic Dermatitis in Childhood. Berkala Ilmu Kesehatan Kulit dan Kelamin. 2015;27(3):176–82.
David Boothe W, Tarbox JA, Tarbox MB. Atopic Dermatitis: Pathophysiology. In: Management of Atopic Dermatitis, Advances in Experimental Medicine and Biology. Texas: Springer International Publishing; 2017. p. 21–37.
Otani T, Furuse M. Tight Junction Structure and Function Revisited. Trends Cell Biol. 2020;30(10):805–17.
Tsukita S, Tanaka H, Tamura A. The Claudins: From Tight Junctions to Biological Systems. Trends Biochem Sci. 2019;44(2):141–52.
Yuki T, Tobiishi M, Kusaka-Kikushima A, Ota Y, Tokura Y. Impaired tight junctions in atopic dermatitis skin and in a skin-equivalent model treated with interleukin-17. PLoS One. 2016;11(9):e0161759.
Furue M, Chiba T, Tsuji G, Ulzii D, Kido-Nakahara M, Nakahara T, et al. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol Int. 2017;66(3):398–403.
Nakahara T, Kido-Nakahara M, Tsuji G, Furue M. Basics and recent advances in the pathophysiology of atopic dermatitis. Journal of Dermatology. 2021;48(2):130–9.
Simpson E, Leung D, Eichenfield L, Boguniewicz. M. Atopic Dermatitis. In: Kang S, Amagai M, Bruckner A, Enk A, Margolis D, McMichael A, et al., editors. Fitzpatrick’s Dermatology 9th edition. New York: McGraw-Hill Education; 2018. p. 363–81.
Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1.
Torres T, Ferreira EO, Gonçalo M, Mendes-Bastos P, Selores M, Filipe P. Update on atopic dermatitis. Acta Med Port. 2019;32(9):606–13.
Kantor R, Silverberg JI. Environmental risk factors and their role in the management of atopic dermatitis. Expert Rev Clin Immunol. 2017;13(1):15–26.
Kuntjoro T, Harijati E. The Pathogenesis of Atopic Dermatitis: The Role of Filaggrin. Berkala Ilmu Kesehatan Kulit dan Kelamin. 2017;29(2):164–7.
Sugita K, Kabashima K. Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases. J Leukoc Biol. 2020;107(5):749–62.
Malik K, Heitmiller KD, Czarnowicki T. An Update on the Pathophysiology of Atopic Dermatitis. Dermatol Clin. 2017;35(3):317–26.
Bergmann S, von Buenau B, Vidal-y-Sy S, Haftek M, Wladykowski E, Houdek P, et al. Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently. Sci Rep. 2020;10(1).
Miyai M, Matsumoto Y, Yamanishi H, Yamamoto-Tanaka M, Tsuboi R, Hibino T. Keratinocyte-Specific Mesotrypsin Contributes to the Desquamation Process via Kallikrein Activation and LEKTI Degradation. J Invest Dermatol. 2014;134(6):1665-74.
Namrata K, Bai BX. Role of Tight Junctions and Their Protein Expression in Atopic Dermatitis. Int J Dermatol Venereol. 2021;4(1):40–4.
de Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-86.e7.
Umborowati MA, Salsabila NW, Damayanti, Anggraeni S, Prakoeswa CRS. The role of skin and gut microbiome in atopic dermatitis. J Pak Assoc Dermatol. 2022;32(1):148–55.