Interleukin (IL)‐33: an orchestrator of immunity from host defence to tissue homeostasis

Abstract

Interleukin (IL)-33, a member of the IL-1 superfamily, functions as an alarm signal, which is released upon cell injury or tissue damage to alert the immune system. It has emerged as a chief orchestrator in immunity and has a broad pleiotropic action that influences differentiation, maintenance and function of various immune cell types via the ST2 receptor. Although it has been strongly associated with immunopathology, critically, IL-33 is involved in host defence, tissue repair and homeostasis. In this review, we provide an overview of the signalling pathway of IL-33 and highlight its regulatory functions in immune cells. Furthermore, we attempt a broader discussion of the emerging functions of IL-33 in host defence, tissue repair, metabolism, inflammatory disease and cancer, suggesting potential avenues to manoeuvre IL-33/ST2 signalling as treatment options.

IL‐33/ST2 axis deficiency exacerbates neutrophil‐dominant allergic airway inflammation

“…IL‐33 has been reported to function as a pleiotropic cytokine involved in immune regulation, host defence, tissue repair and metabolic homeostasis 40 . IL‐33/ST2 signalling plays a vital role in asthma, especially in the setting of a type 2 inflammatory response 41 .…”

IL-33/ST2 Axis Deficiency Exacerbates Hepatic Pathology by Regulating Treg and Th17 Cells in Murine Schistosomiasis Japonica

“…3,8 The alarmin IL-33 has been reported to function as a pleiotropic cytokine involved in immune regulation, host defense, tissue repair and metabolic homeostasis. 45 However, the role of IL-33 remains controversial in different schistosomiasis settings. [20][21][22] Therefore, more comprehensive exploration and deeper understanding of the IL-33/ST2 pathway especially in the peak of immunopathology during Schistosoma infection are required.…”

The curious case of IL‐33 in homeostasis and infection

“…Accordingly, signaling via the ST2 receptor leads to differentiation, maintenance, and effector function of several immune cells [4–7]. In line with this, recent research has described a central role for IL‐33 in tumor immunity, metabolic disease, inflammation, and infection [4–8].…”

“…Several types of immune cells, including granulocytes, dendritic cells (DCs), macrophages, type 2 innate lymphoid cells (ILC2s), activated T cells and B cells, natural killer (NK) cells, NK T cells, and regulatory T cells (T REGs ), feature ST2 expression [5]. Accordingly, signaling via the ST2 receptor leads to differentiation, maintenance, and effector function of several immune cells [4][5][6][7]. In Correspondence: Dr. Ramon Arens and Dr. Reza Nadafi e-mail: r.arens@lumc.nl line with this, recent research has described a central role for IL-33 in tumor immunity, metabolic disease, inflammation, and infection [4][5][6][7][8].…”