Role of IL-33/ST2 Pathway in Inflammatory Bowel Disease: An Overview and Future Perspectives

Author:

Giordano Walter1ORCID,Ricciardi Gabriele12ORCID,Casciaro Marco3ORCID,Fiorentino Vincenzo4ORCID,Pizzimenti Cristina4ORCID,Viola Anna5,Martini Maurizio4ORCID,Tuccari Giovanni4ORCID,Ieni Antonio4

Affiliation:

1. Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98125 Messina, Italy

2. Multi-Specialist Clinical Institute for Orthopaedic Trauma Care (COT), 98124 Messina, Italy

3. Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University Hospital of Messina, 98125 Messina, Italy

4. Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98125 Messina, Italy

5. Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy

Abstract

Inflammatory bowel disease (IBD) represents a heterogenous and complex group of idiopathic chronic inflammatory conditions affecting the gastrointestinal tract and other extraintestinal systems with rising global incidences. The interplay of genetic predisposition and environmental factors contributes to its pathogenesis. Among the key cytokines implicated in IBD molecular alterations, IL-33 stands out for its multifaceted roles in both pathogenesis and repair mechanisms. IL-33, known for its action in initiating immune responses, is closely associated with Th2 immunity and is considered a potent inflammatory factor with dual functions, acting both as a pro-inflammatory cytokine and a transcriptional regulator. Primarily expressed by non-hematopoietic cells in the gastrointestinal tract, IL-33 interacts with its receptor, ST2, to modulate immune responses. In IBD, dysregulated IL-33 expression exacerbates mucosal inflammation, compromising barrier integrity and promoting tissue damage and fibrosis. Additionally, IL-33 plays a complex role in IBD-related colorectal cancer (CRC), affecting tumor progression and angiogenesis. This review summarizes the multifaceted roles of IL-33 in gastrointestinal health and disease, emphasizing its significance in the pathogenesis of IBD and CRC. Moreover, we thought it of interest to provide new insights into potential therapeutic avenues targeting IL-33 signaling for the management of these debilitating conditions.

Publisher

MDPI AG

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