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Review
. 2021 Nov 3;10(11):3000.
doi: 10.3390/cells10113000.

Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis

Milena Iwaszko  1 , Sylwia Biały  1 , Katarzyna Bogunia-Kubik  1
Affiliations
Review

Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis

Milena Iwaszko et al. Cells. .

Abstract

Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.

Keywords: IL-13; IL-4; ankylosing spondylitis; inflammatory arthritis; psoriatic arthritis; rheumatoid arthritis; spondyloarthritis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
IL-4 receptor alpha (IL-4Rα) constitutes subunits of two heterodimeric receptors, named type I and type II receptors. The type I receptor, composed of IL-4Rα and common cytokine receptor γ-chain (γc), interacts only with IL-4. The type II receptor is formed from IL-4Rα and IL-13Rα1 subunits and interacts with either IL-13 or IL-4. IL-13 also displays the capacity to bind IL-13Rα2, which is regarded as a decoy receptor. A binding of a ligand by type I and II receptors results in an activation of Janus family kinases (JAK1, JAK2, and JAK3) followed by phosphorylation of a signal transducer and activator transcription 6 (STAT6).
Figure 2
Figure 2
Macrophages’ polarization upon the action of IL-4 and IL-13 from classically activated/inflammatory (M1) phenotype to alternatively activated (M2) phenotype.
Figure 3
Figure 3
IL-4/IL-13 functions in inflammatory arthritis.
See this image and copyright information in PMC

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