Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis

Abstract

Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)-driven disease. Interleukin (IL)-4 and IL-13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor-associated signal transduction machinery such as Janus kinases. Recently, IL-13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL-4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL-13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL-13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD.

Interleukin-25-Mediated Resistance Against Intestinal Trematodes Does Not Depend on The Generation of Th2 Responses

“…IL-13 binds 13R 1 which complexes with IL-4R to form the type 1 receptor signaling, but IL-13 also binds the cell surface and soluble forms of the monomeric type 2 receptor (IL-13R 2 chain). However, IL-13R 2 has a decoy effect, lacking signal transduction machinery and limiting the activity of IL-13 since binds the cytokine making it unavailable for activating type 1 receptor [36][37][38][39]. Herein, we have shown that rIL-13R 2 chain limits the ability of mice to respond to E. caproni primary infection, even in the presence of rIL-25.…”

Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses

“…IL-13 binds 13R1 which complexes with IL-4R to form the type 1 receptor signaling, but IL-13 also binds the cell surface and soluble forms of the monomeric type 2 receptor (IL-13R2 chain). However, IL-13R2 has a decoy effect, lacking signal transduction machinery and limiting the activity of IL-13 since binds the cytokine making it unavailable for activating type 1 receptor[37][38][39][40].…”

Cytokines Profile (Il-4, Il-13) of Children With Severe Forms of Atopic Dermatitis Versus Other Grades of Severity

“…Atopy is a genetic predisposition to develop allergic symptoms caused by environmental antigens (allergens). Numerous studies indicate that two of the key cytokines are interleukin-4 (IL-4) and IL-13 [1,3]. They are potent mediators of the induction and effector phases of the Th-2 immune response.…”

“…Early studies strongly suggested that AD is also linked to Innate lymphoid cells2 (ILC2) dysregulation. ILC2 express pro-allergic mediators IL-4, IL-5, IL-9, IL-13 [1,16]. It was proved that in comparison to CD4+, ILC2 are capable of producing IL-5 and IL-13 cytokines per-cell in case of allergic inflammation against house dust-mite independently.…”

“…Researchers have assumed that IL-13 promotes inflammation in the periphery, and IL-4 has a central effect. Up to date studies have shown a significant data of increased cytokine IL-13 expression in AD patients (in affected skin areas) and normal IL-13 level in healthy people, however, there were no significant changes in IL-4 levels [1]. Elevated levels of IL-13 were correlated with the severity of AD due to the SCORAD scale [2,9].…”