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Scleroderma
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
The interleukin-13 pathway in the skin has also been reported to be involved in diffuse SSc. In particular, a seminal paper reported on the comparison of human and murine scleroderma that demonstrated that IL-13 and CCL2 are disease-specific targets (68). The chemokine gene CCL2 levels highly correlated with mRSS and IL-13 levels.
Airway Wall Remodelling in the Pathogenesis of Asthma: Cytokine Expression in the Airways
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Peter Bradding, Anthony E. Redington, Stephen T. Holgate
Recently, a further cytokine, designated interleukin-13, has been identified which is able to support the synthesis of IgE by human48 and murine B-lymphocytes in vitro independently of IL-4. This cytokine is encoded as part of the IL-4 gene cluster on chromosome 5 and shares approximately 30% homology at the amino acid level with IL-4 itself.49 It also shares many properties with IL-4, including the ability to increase the expression of CD23 on resting B-lymphocytes and to stimulate B-lymphocyte proliferation,48,50 but unlike IL-4 it has no known effects in relation to T cells. The actions of IL-13 are mediated through a discrete receptor which shares a signal-transducing component with the IL-4 receptor.51 In mice, the failure of most IL-4 “knockout” animals to synthesise any IgE46 suggests that IL-13 alone is insufficient to support this process in vivo, whereas in humans this remains to be established.
Cancer
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Advanced cancer therapies also include the use of tissue-specific cytotoxic agents. For example, novel mutagenic cytotoxins (interleukin 13 (IL-13)) have been developed against brain tumors, which do not interact with receptors of the normal tissue but only with brain gliomas.
Investigational anti IL-13 asthma treatments: a 2023 update
Published in Expert Opinion on Investigational Drugs, 2023
Maria Gabriella Matera, Josuel Ora, Luigino Calzetta, Paola Rogliani, Mario Cazzola
Interleukin-13 (IL-13) is a pleiotropic cytokine produced by type-2 helper T-cells (TH2), B lymphocytes, CD8+ cells, type (T)2 innate lymphoid cells, alveolar macrophages, human mast cells, and basophils [1]. It shares with IL-4 a receptor known as a type II receptor (IL-4RII) [2]. This receptor is a heterodimer composed of an IL-4 receptor subunit (IL-4 Rα) and an IL-13 receptor subunit (IL-13 Rα1). IL-13 Rα1 binds IL-13 with low affinity. IL-13 Rα1 associates with tyrosine kinase (TYK)2 or Janus kinase (JAK)2, whereas IL-4 Rα1 activates JAK1 [3]. Both receptor complexes promote the phosphorylation of signal transducer and activator of transcription (STAT)-6 and subsequent translocation to the nucleus, where it induces the transcription of IL-4 responsive genes involved in TH2 response [4]. However, the potency and kinetics of the two cytokines vary. IL-4 works more quickly and with lower doses than IL-13, but the higher total concentration of IL-13R1 relative to IL-4 R seems to allow a high concentration of IL-13 to signal more powerfully than IL-4 [5]. This interaction may activate other signaling pathways, including STAT-3, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase [2]. B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes express the IL-4RII complex [6].
Targeting interleukin-13 receptor α2 (IL-13Rα2) for glioblastoma therapy with surface functionalized nanocarriers
Published in Drug Delivery, 2022
Ruijia Liang, Cheng Wu, Shiming Liu, Wenyan Zhao
Interleukin-13 (IL-13) during normal and pathological conditions particularly cancer plays a versatile role in regulating immune environment and responses as well (Chu et al., 2020; Yuan et al., 2022). It has been reported that IL-13 in majority of cells binds with a low affinity monomer (IL13Rα1) followed by IL4Rα forming a complex heterodimer. Further, the resultant complex results in the activation of transcription factors and signal transducers through release of Janus kinases (Pham et al., 2019). In addition to low affinity receptors, IL-13 also binds to high affinity receptors such as IL13Rα2 in cancer cells (Okamoto et al., 2019). The IL13Rα2 gene RNA transcripts encode 380 amino acid proteins and are expressed in normal cells sparsely (Izuhara et al., 2007). While in glioblastoma multiform, IL13Rα2 offers expression for about 30,000 binding sites (Sharma & Debinski, 2018).
Association of Dupilumab with Intraocular Inflammation
Published in Ocular Immunology and Inflammation, 2022
Sneha Padidam, Veena Raiji, Ramana Moorthy, Armando Oliver, Brian Do
Dupilumab (Dupixent, Regeneron, USA) is a human monoclonal antibody that dually inhibits interleukin-4 and interleukin-13 via IL4-receptor α blockade. It has been approved by the United States Food & Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis and asthma.1 These are chronic T-cell (Th2) mediated inflammatory diseases in which interleukin-4 and interleukin-13 are upregulated.2 Studies evaluating dupilumab have found it to effectively decrease atopic dermatitis disease burden as well as improve health-related quality of life for patients with atopic dermatitis.3Additionally, it has been shown to reduce the risk of severe asthma exacerbations, especially in patients with an eosinophilic phenotype and oral corticosteroid-dependent asthma.4