@article { author = {Furue, Masutaka and Ulzii, Dugarmaa and Vu, Yen and Tsuji, Gaku and Kido-Nakahara, Makiko and Nakahara, Takeshi}, title = {Pathogenesis of Atopic Dermatitis: Current Paradigm}, journal = {Iranian Journal of Immunology}, volume = {16}, number = {2}, pages = {97-107}, year = {2019}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {10.22034/iji.2019.80253}, abstract = {Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal roles in atopic inflammation. The expression of IL-4 and IL-13 as well as type 2 chemokines such as CCL17, CCL22 and CCL26 is increased in the lesional skin of AD. In addition, IL-4 and IL-13 down-regulate the expression of filaggrin in keratinocytes and exacerbate epidermal barrier dysfunction. Keratinocytes in barrier-disrupted epidermis produce large amounts of thymic stromal lymphopoietin, IL-25 and IL-33, conducing to type 2 immune deviation via OX40L/OX40 signaling. IL-31, produced by type 2 T cells, is a cardinal pruritogenic cytokine. IL-4 and IL-13 also amplify the IL-31-mediated sensory nerve signal. These molecules are particularly important targets for future drug development for AD.}, keywords = {Atopic Dermatitis,IL-4,IL-13,IL-31,OX40}, url = {https://iji.sums.ac.ir/article_44935.html}, eprint = {https://iji.sums.ac.ir/article_44935_c53608540ed3579a71fb27ceee4a5e68.pdf} }