Immune Netw.  2022 Feb;22(1):e11. 10.4110/in.2022.22.e11.

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

• Ham J
• Shin JW
• Ko BC
• Kim HY

• KMID: 2536229
• DOI: http://doi.org/10.4110/in.2022.22.e11

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 epitheliumderived 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.

Keyword

Alarmins; Hypersensitivity; Autoimmune disease; Biological therapy