Commentary: IL-4 and IL-13 receptors and signaling

McCormick, Sarah; Heller, Nicola

doi:10.1016/j.cyto.2015.05.023

Cited by 268 publications

(264 citation statements)

References 180 publications

(173 reference statements)

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“…Furthermore, IL-13 is not only produced by T H 2 cells, but can also be generated by invariant NK T cells (iNKT), granulocytes (e.g. basophils, eosinophils, and mast cell), murine group 2 innate lymphoid cells (ILC2s), and human ‘Chemoattractant Receptor-homologous molecule expressed on T H 2 lymphocytes’ (CRTH2)-type 2 ILCs (309–313). It is structurally similar to IL-4 and signals through cell surface receptor heterodimers composed of IL-4Rα and IL-13Rα1 subunits to activate STAT6 (313).…”

Section: Cytokinesmentioning

confidence: 99%

“…basophils, eosinophils, and mast cell), murine group 2 innate lymphoid cells (ILC2s), and human ‘Chemoattractant Receptor-homologous molecule expressed on T H 2 lymphocytes’ (CRTH2)-type 2 ILCs (309–313). It is structurally similar to IL-4 and signals through cell surface receptor heterodimers composed of IL-4Rα and IL-13Rα1 subunits to activate STAT6 (313). Though not much is known regarding IL-13 in Mtb infection, whole blood mRNA from latently infected children shows increased IL-13 compared to uninfected controls (314), although IL-13 levels are not different between actively and latently infected children (314).…”

Section: Cytokinesmentioning

confidence: 99%

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Cytokines and Chemokines inMycobacterium tuberculosisInfection

et al. 2016

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Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis -infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development. Much of the data highlighted in this review appears at first glance to be contradictory, but it is the balance between the cytokines and chemokines that is critical, and the “goldilocks” (not too much and not too little) phenomenon is paramount in any discussion of the role of these molecules in TB. Determination of how the key chemokines/cytokines and their receptors are balanced and how the loss of that balance can promote disease is vital to understanding TB pathogenesis and to identifying novel therapies for effective eradication of this disease.

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Section: Cytokinesmentioning

confidence: 99%

Section: Cytokinesmentioning

confidence: 99%

Cytokines and Chemokines inMycobacterium tuberculosisInfection

et al. 2016

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“…In theory, every cell has the potential to respond to IL-4, IL-13 or both, but some cell types seem to be more susceptible [11]. …”

Section: The Role Of Il-13 and Il-4mentioning

confidence: 99%

A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma

Bagnasco

Ferrando

Varricchi

et al. 2016

Int Arch Allergy Immunol

190

126

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Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma. IL-13 and IL-4 partly share the same receptor and signaling pathways and both are deeply involved in immunoglobulin E (IgE) synthesis, eosinophil activation, mucus secretion and airways remodeling. Several anti-IL-13 strategies have been proposed (anrukinzumab, lebrikizunab and tralokinumab), with relevant clinical results reported with lebrikizumab. Such studies facilitate better definition of the possible predictive markers of response to a specific treatment (e.g. eosinophils, total IgE, fraction of exhaled nitric oxide and periostin). In parallel, anti-IL-4 strategies have been attempted (pascolizumab, pitakinra and dupilumab). So far, dupilumab was reported capable of reducing the severity of asthma and the rate of exacerbations. IL-13 and IL-4 are crucial in TH2-mediated inflammation in asthma, but it remains clear that only specific endotypes respond to these treatments. Although the use of anti-IL-14 and anti-IL-13 strategies is promising, the search for appropriate predictive biomarkers is urgently needed to better apply biological treatments.

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“…[10] IL-4R activation leads to STAT-6 phosphorylation as primary signaling pathway [11] ,w hich induces reporter gene expression. Both IL-4 muteins were as active as wt-IL-4 in all cell culture setups, therebye stablishing Lys42 as as uitable insertion site for generating active IL-4 muteins with site-specific anchors ites ( Figure 3A-C).…”

mentioning

confidence: 99%

Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization

et al. 2016

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Driving macrophage (Mϕ) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin-4 (IL-4) promotes polarization into the M2-Mϕ phenotype, but its systemic use is constrained by dose-limiting toxicity. Consequently, we developed IL-4-decorated surfaces aiming at sustained and localized activity. IL-4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell-stimulation ability and binding affinity to IL4Rα similar to those of wt-IL-4. Copper-catalyzed (CuAAC) and copper-free strain-promoted (SPAAC) 1,3-dipolar azide-alkyne cycloadditions were used to site-selectively anchor IL-4 to agarose surfaces. These surfaces had sustained IL-4 activity, as demonstrated by TF-1 cell proliferation and M2, but not M1, polarization of M-CSF-generated human Mϕ. The approach provides a blueprint for the engineering of cytokine-activated surfaces profiled for sustained and spatially controlled activity.

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Commentary: IL-4 and IL-13 receptors and signaling

Cited by 268 publications

References 180 publications

Cytokines and Chemokines inMycobacterium tuberculosisInfection

Cytokines and Chemokines inMycobacterium tuberculosisInfection

A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma

Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization

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