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Cytokine Network

  • Kenji IzuharaEmail author
  • Satoshi Nunomura
  • Shoichiro Ohta
  • Masahiro Ogawa
  • Yasuhiro Nanri
Chapter

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.

Keywords

Cytokine Type 2 inflammation TH22 cell Epithelial cell-derived cytokine Dupilumab 

Notes

Acknowledgments

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

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Kenji Izuhara
    • 1
    Email author
  • Satoshi Nunomura
    • 1
  • Shoichiro Ohta
    • 1
  • Masahiro Ogawa
    • 1
  • Yasuhiro Nanri
    • 1
  1. 1.Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical SchoolSagaJapan

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