Researchers investigated the role of a molecule, interleukin (IL)-33, in a skin psoriasis mouse model to further understand the role of this cytokine in inflammatory diseases. The findings suggest the molecule is not required for arthritis development in psoriasis, which indicates it is not essential for development of chronic inflammation.
The research paper, “Collagen-induced arthritis and imiquimod-induced psoriasis develop independently of interleukin-33,” was published in Arthritis Research & Therapy.
IL-33 is localized in the cell nucleus and was first described as a cytokine passively released by damaged dying epithelial and endothelial cells. The expression pattern of IL-33 receptor indicates that it is in the center of a complex cellular network of immune and non-immune cells that can both promote and reduce inflammation depending on the tissue and cytokine environment.
As psoriasis is a chronic inflammatory disease, IL-33 may have a role in its development. IL-33 level is increased in skin lesions of patients with psoriasis and decreased after anti-TNF-α treatment.
In the study, researchers studied the impact of IL-33 deficiency in two animal models of chronic inflammation. Researchers have shown that administration of IL-33 could inhibit collagen-induced arthritis in mice. However, its pathophysiological role in arthritis remained mostly unclear.
To further understand the role of internal IL-33 in inflammatory diseases, researchers also studied its role in a skin psoriasis model. The mice models, which were deficient in IL-33 in a way that the IL-33 gene could be activated by an external substance, allowed researchers to induce or block the IL-33 gene expression. Psoriasis type dermatitis was induced by applying imiquimod to the skin of mice.
Although IL-33 is expressed in the synovium of arthritic mice and human keratinocytes (epidermal cells), IL-33 is not needed for the development of collagen-induced arthritis or psoriasis. Its absence does not disturb the development of T-cell subpopulations.
Altogether, the data demonstrated that exogenous IL-33 can nearly completely block collagen-induced arthritis development, suggesting that this cytokine is not crucial for the development of chronic inflammation. Further studies of arthritis patients are necessary to confirm whether a therapeutic approach targeting the IL-33/ST2 signaling pathways would be effective.