Targeting the IL-33/ST2 signalling pathway as a therapeutic strategy for the treatment of multiple inflammatory diseases
DOI:
https://doi.org/10.60988/p.v37i2S.280Keywords:
interleukin-33; ST2 receptor; IL-33/ST2 pathway; therapeutic strategy; inflammatory diseasesAbstract
Interleukin-33 (IL-33) is a cytokine belonging to the interleukin-1 (IL-1) superfamily. It is expressed and upregulated following pro-inflammatory stimulation, and plays a key role in inducing the synthesis of T-helper type 2 (Th2) cytokines and IN promoting the pathogenesis of Th2-related diseases. IL-33 exerts its biological effects by binding to its receptor, ST2; a member of the IL-1 receptor family that exists in two isoforms: the transmembrane form (ST2L) and the soluble form (sST2). Through ST2L, IL-33 signals surrounding immune cells in response to tissue injury. In the respiratory system, IL-33 overexpression can exacerbate chronic respiratory diseases. In the cardiovascular system, cardiomyocytes and cardiac fibroblasts increase the expression of both IL-33 and ST2. Within the central nervous system, IL-33 promotes M2 macrophage polarization and/or regulatory T cell (Treg) activation, thereby contributing to an anti-inflammatory response in various disease contexts. In the renal system, IL-33/ST2 signalling has been implicated in both pathogenic and tissue-protective processes across multiple renal disorders. In the gastrointestinal tract, targeting the IL-33 signalling pathway presents a potential therapeutic strategy. In type 2 diabetes mellitus, metformin treatment has revealed a key role for IL-33 and ST2 in disease modulation. In skin diseases such as psoriasis and vitiligo, increased IL-33 expression has been observed in lesional tissues. Finally, in rheumatological diseases, the IL-33/ST2 pathway appears to exert a detrimental influence during both early and advanced disease stages.
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