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Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside

  • Jongho Ham (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Jae Woo Shin (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Byeong Cheol Ko (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Hye Young Kim (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2021.12.30
  • Accepted : 2022.02.15
  • Published : 2022.02.28
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Abstract

When epithelial cells are exposed to potentially threatening external stimuli such as allergens, bacteria, viruses, and helminths, they instantly produce "alarmin" cytokines, namely, IL-33, IL-25, and TSLP. These alarmins alert the immune system about these threats, thereby mobilizing host immune defense mechanisms. Specifically, the alarmins strongly stimulate type-2 immune cells, including eosinophils, mast cells, dendritic cells, type-2 helper T cells, and type-2 innate lymphoid cells. Given that the alarm-raising role of IL-33, IL-25, and TSLP was first detected in allergic and infectious diseases, most studies on alarmins focus on their role in these diseases. However, recent studies suggest that alarmins also have a broad range of effector functions in other pathological conditions, including psoriasis, multiple sclerosis, and cancer. Therefore, this review provides an update on the epithelium-derived cytokines in both allergic and non-allergic diseases. We also review the progress of clinical trials on biological agents that target the alarmins and discuss the therapeutic potential of these agents in non-allergic diseases.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (2019R1A2C2087574 and SRC 2017R1A5A1014560).

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