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Evolution of Atopic Dermatitis in the 21st Century

Abstract

Immune dysregulation, barrier defects, and increased skin infections combine to lead to the onset of atopic dermatitis (AD). It was previously thought that type 2 inflammation was dominant in the acute phase of AD, and then in the chronic phase, it became type 1 inflammation. However, it is now widely accepted that both type 2 inflammation and inflammation induced by TH22 cells are dominant in both the acute and chronic phases of AD. In type 2 inflammation, IL-4, IL-13, and IL-5, which are signature type 2 cytokines, are highly expressed and are involved in forming the characteristic features of AD. Epithelial cell-derived cytokines—thymic stromal lymphopoietin, IL-33, and IL-25—initiate type 2 inflammation by controlling various cells, including group 2 innate lymphoid cells. Moreover, IL-31, a newly identified type 2 cytokine, induces itch by acting on sensory neurons. IL-22, a signature cytokine derived from TH22 cells, is significantly expressed in AD skin and is believed to contribute to the pathogenesis of AD as well as type 2 cytokines by acting on keratinocytes. Based on both basic and clinical findings, several antibodies targeting cytokines have been developed as therapeutic agents against AD, among which dupilumab, targeting the IL-4 receptor α chain shared with IL-4R and IL-13R, has become the first molecularly targeted drug for the treatment of AD.

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Acknowledgments

We thank Dr. Dovie R. Wylie for her critical review of this manuscript.

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Authors and Affiliations

  1. Division of Medical Biochemistry, Department of Biomolecular Sciences, , Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Kenji Izuhara, Satoshi Nunomura, Shoichiro Ohta, Masahiro Ogawa & Yasuhiro Nanri

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  1. Kenji Izuhara
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  2. Satoshi Nunomura
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  3. Shoichiro Ohta
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  4. Masahiro Ogawa
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  5. Yasuhiro Nanri
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Correspondence to Kenji Izuhara .

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Editors and Affiliations

  1. Department of Dermatology, Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Ichiro Katayama

  2. Department of Dermatology, Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Hiroyuki Murota

  3. Department of Dermatology, National Defense Medical College, Tokorosazawa, Saitama, Japan

    Takahiro Satoh

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Izuhara, K., Nunomura, S., Ohta, S., Ogawa, M., Nanri, Y. (2018). Cytokine Network. In: Katayama, I., Murota, H., Satoh, T. (eds) Evolution of Atopic Dermatitis in the 21st Century. Springer, Singapore. https://doi.org/10.1007/978-981-10-5541-6_9

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