Airway Wall Remodelling in the Pathogenesis of Asthma: Cytokine Expression in the Airways
Alastair G. Stewart in AIRWAY WALL REMODELLING in ASTHMA, 2020
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.
Anisakis
Dongyou Liu in Laboratory Models for Foodborne Infections, 2017
As cited before, contact dermatitis is one of the consequences of antigen exposure to Anisakis proteins in seafood-processing workers. Therefore, to understand the basic mechanisms in the development of allergic sensitization through the skin, repeated epicutaneous exposure of Anisakis proteins in wild-type (WT), IL-4-, IL-4Rα-, IL-13-, and IL-4/IL-13-deficient mice was evaluated by following the systemic signs and symptoms. Epicutaneous sensitization with Anisakis larval antigens induced the WT localized inflammation, epidermal hyperplasia, production of TH2 cytokines, antigen-specific IgE and IgG1, and anaphylactic shock after intravenous challenge. IL-13-deficient mice failed to develop epidermal hyperplasia and inflammation, and in IL-4-, IL-4/IL-13-, and IL-4Rα-deficient mice, anaphylaxis was reduced. These results suggest that interleukin-13 plays a central role in contact dermatitis development, whereas IL-4 drives the Th2 profile and resultant anaphylactic reactions.48
Genetics and Asthma
Jonathan A. Bernstein, Mark L. Levy in Clinical Asthma, 2014
Recent genome-wide association study (GWAS) approaches have identified several genes or loci that are associated with asthma susceptibility,1–4 including the ORM1-like 3/gasdermin-like (ORMDL3/GSDML) region of chromosome 17q21, interleukin 33 (IL-33) and its receptor interleukin 1 receptor-like 1 isoform 1 (IL-1RL1), thymic stromal lymphopoietin (TSLP), the major histocompatibility (MHC) region on 6p21, and interleukin 13 (IL-13). Some of these genes have previously been linked to asthma or other related allergic phenotypes in earlier candidate gene or positional cloning studies, suggesting that shared inflammatory pathways may be affected. For example, the MHC region was one of the first asthma susceptibility loci identified5 and it appears to play a major role in asthma and allergen sensitization.3 Regulatory T cell signaling genes, such as the SMAD family member 3 (SMAD3), encoding a transcriptional modulator related to transforming growth factor β, may also play a critical role in the development of asthma. A number of these susceptibility genes have been replicated in some but not all populations, suggesting that there may be heterogeneity in the genetic risk in populations of different ethnic backgrounds. The results from major GWAS and meta-analyses of asthma reviewed in this chapter are summarized in Table 3.1.
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).
Higher Peripheral Blood IFN-γ-/IL-4+ Th2 Lymphocytes Are Associated with Lower Rate of Relapse in Patients with Lymphoma
Published in Immunological Investigations, 2022
Mehdi Dehghani, Mani Ramzi, Mehdi Kalani, Hossein Golmoghaddam, Nargess Arandi
The significance of CD4+ T helper cell subsets in orchestrating and fine-tuning the sustained anti-tumor immune response has been debated for many decades. The interplay between CD4+ T-helper and tumor cells can affect tumor growth leading to tumor cell eradication or progression (de Lima et al. 2020; Spacek et al. 2018). However, most of the tumor cells exploit various immune-escape mechanisms to evade from efficient recognition by these CD4+ T cells. Upon antigenic stimulation, the activated CD4+ T cells are differentiated into different CD4+ T cell subsets, a process that is controlled by unique sets of transcription factors and cytokine produced during the immune reaction (Chraa et al. 2019; Dobrzanski 2013). T-helper 1 (Th1) cells are a group of CD4+ T cells that produce interferon-gamma (IFN-γ) and have an indispensable role in eliciting an anti-tumor immune response. Whereas, T-helper 2 (Th2) lymphocytes produce interleukin-4 (IL-4) and interleukin-13 (IL-13) that are responsible for humoral immunity and antibody production (Chraa et al. 2019; Dobrzanski 2013). While the central role of the Th1 cells in the anti-tumor immune response is well defined, the Th2 subgroup might have an ambivalent role in human cancers like solid tumors (Chraa et al. 2019; Dobrzanski 2013). Also, these CD4+ T cell subpopulations might exhibit differential functions in hematologic malignancies.
Related Knowledge Centers
- Basophil
- Cd4
- Interleukin 4
- Protein
- T Helper Cell
- Cytokine
- Mast Cell
- Gene
- Natural Killer T Cell
- Eosinophil