Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

Abstract

Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.

Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model

“…It should be noted, however, that the Conv (Rm2) showed relatively high upregulation of IL-25. It is known that IL-25 can be produced by Th2 cells along with ILC2s, macrophages and other monocytes, which may be a reason for upregulation of this cytokine in these mice ( 84 ).…”

Skin Immunosenescence and Type 2 Inflammation: A Mini-Review With an Inflammaging Perspective

“…IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) released from damaged epithelium directly activate the production of IL-4, 5, 9, 13, and 31 from ILC2 and Th2 cells, thus characterizing type 2 inflammation immunity ( Akdis, et al, 2020 ). Both IL-25 and IL-33 can activate MAPK and NK-κB signaling pathways via binding to IL-17RA/B and IL-1 receptor-like 1 (IL1RL1), respectively ( Akdis, et al, 2020 ; Deng, et al, 2021 ). By activating signal transducer and activator of transcription (STAT), skin LC/DC-derived and keratinocyte-derived TSLP are critical for Th2-type immune responses and mediating pruritus exacerbation, respectively ( Kim et al, 2013 ).…”

Targeting Downstream Type 2 Cytokines or Upstream Epithelial Alarmins for Severe Asthma

“…43 TH17 cells predominantly exert their action by producing the IL-17 family of cytokines (IL-17A-17F), of which IL-17A and IL-25 (IL-17E) are thought to play pivotal roles in pulmonary inflammation through IL-17RA-containing heterodimeric receptor complexes expressed in airway smooth muscle cells. 43 In a phase 2a RCT studying the anti-IL-17RA monoclonal antibody brodalumab, which blocks IL-17A, IL-17F, and IL-17E (IL-25), no improvements were observed in the primary end point of ACQ after 12 weeks of treatment in patients with inadequately controlled moderate-to-severe asthma. 44 Any improvements in the secondary end point of FEV 1 also did not amount to statistical significance or a clinically meaningful response.…”