IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

Saluja, Rohit; Zoltowska, Anna; Ketelaar, Marjolijn; Nilsson, Gunnar

doi:10.1016/j.ejphar.2015.04.047

Cited by 50 publications

(55 citation statements)

References 128 publications

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“…Since IL-33 has several prominent effects on mast cell functions 23 , we explored if IL-33 exposure in sensitized mice would lead to mast cell expansion in the lung. IL-33 treatment showed a tendency, though not statistically significant, to increase the number of mast cells, both in sham sensitized mice as well as in OVA sensitized mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interleukin 33 exacerbates antigen driven airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma

Sjöberg

Nilsson

Lei

et al. 2017

Sci Rep

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Interleukin 33 (IL-33) represents a potential link between the airway epithelium and induction of Th2-type inflammatory responses associated with the development of asthma. This study investigated the potential of IL-33 to exacerbate antigen driven asthma responses. An ovalbumin (OVA) asthma model was used in which sensitized C57BL/6 mice were exposed to IL-33 before each OVA challenge. IL-33 given to sensitized mice acted synergistically with antigen and aggravated airway inflammation, hyperresponsiveness and remodeling compared with mice that were only OVA sensitized and challenged and mice that were only exposed to IL-33. Elevated levels of local and systemic mast cell protease mMCP-1, as well as antigen-specific IgE production, were observed following IL-33 administration to sensitized mice. Similarly, exposing OVA-sensitized mice to IL-33 increased the Th2 cytokine levels, including IL-4, IL-5 and IL-13. Furthermore, IL-33 and OVA administration to OVA-sensitized mice increased ILC2s in the lung, suggesting a role for ILC2s in IL-33-mediated exacerbation of OVA-induced airway responses. Collectively, these findings show that IL-33 aggravates important features of antigen-driven asthma, which may have implications for asthma exacerbations.

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Section: Resultsmentioning

confidence: 99%

Interleukin 33 exacerbates antigen driven airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma

Sjöberg

Nilsson

Lei

et al. 2017

Sci Rep

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show abstract

“…Two examples among the uncovered MC “private genes” are T1/ST2 ( IL1RL1 ) and MRGPRX2 [1], the former encoding the IL-33 receptor [35], the latter a G protein coupled receptor mediating so-called “pseudo-allergic” reactions [36]. Here, we investigated their modulation by RA.…”

Section: Resultsmentioning

confidence: 99%

Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability

Babina

Artuc

Guhl

et al. 2017

IJMS

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The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays. We found that while MC size and granularity remained unchanged, RA potently interfered with MC proliferation. Conversely, a modest survival-promoting effect from RA was noted. The granule constituents, histamine and tryptase, remained unaffected, while RA had a striking impact on MC chymase, whose expression dropped by gene and by peptidase activity. The newly uncovered MRGPRX2 performed similarly to chymase. Intriguingly, RA fostered allergic MC degranulation, in a way completely uncoupled from FcεRI expression, but it simultaneously restricted MRGPRX2-triggered histamine release in agreement with the reduced receptor expression. Vitamin-A-derived hormones thus re-shape skin-derived MCs numerically, phenotypically, and functionally. A general theme emerges, implying RA to skew MCs towards processes associated with (allergic) inflammation, while driving them away from the skin-imprinted MCTC (“MCs containing tryptase and chymase”) signature (chymase, MRGPRX2). Collectively, MCs are substantial targets of the skin retinoid network.

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“…IL‐33 activates mast cells, leading to secretion of cytokines and lipid mediators, and potentiates degranulation in response to FcεRI triggering . Not only does IL‐33 increase the percentage of mast cells that degranulate, but also the magnitude of degranulation at a single cell level .…”

Section: Multifunctional Roles Of Il‐33 In Mast Cell Signalingmentioning

confidence: 99%

“…IL-33 activates mast cells, leading to secretion of cytokines and lipid mediators, 76,77 and potentiates degranulation in response to FcεRI triggering. [77][78][79][80] Not only does IL-33 increase the percentage of mast cells that degranulate, but also the magnitude of degranulation at a single cell level. 81 Antigen/IgE-mediated degranulation is also increased by IL-6, but to a lesser extent than by IL-33, and combining IL-33 and IL-6 has a synergistic effect.…”

Section: Multifunctional Roles Of Il-33 In Mast Cell Signalingmentioning

confidence: 99%

Changing the threshold—Signals and mechanisms of mast cell priming

Hálová

Rönnberg

Dráberová

et al. 2018

Immunological Reviews

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Mast cells play a key role in allergy and other inflammatory diseases involving engagement of multivalent antigen with IgE bound to high-affinity IgE receptors (FcεRIs). Aggregation of FcεRIs on mast cells initiates a cascade of signaling events that eventually lead to degranulation, secretion of leukotrienes and prostaglandins, and cytokine and chemokine production contributing to the inflammatory response. Exposure to pro-inflammatory cytokines, chemokines, bacterial and viral products, as well as some other biological products and drugs, induces mast cell transition from the basal state into a primed one, which leads to enhanced response to IgE-antigen complexes. Mast cell priming changes the threshold for antigen-mediated activation by various mechanisms, depending on the priming agent used, which alone usually do not induce mast cell degranulation. In this review, we describe the priming processes induced in mast cells by various cytokines (stem cell factor, interleukins-4, -6 and -33), chemokines, other agents acting through G protein-coupled receptors (adenosine, prostaglandin E , sphingosine-1-phosphate, and β-2-adrenergic receptor agonists), toll-like receptors, and various drugs affecting the cytoskeleton. We will review the current knowledge about the molecular mechanisms behind priming of mast cells leading to degranulation and cytokine production and discuss the biological effects of mast cell priming induced by several cytokines.

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IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

Cited by 50 publications

References 128 publications

Interleukin 33 exacerbates antigen driven airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma

Interleukin 33 exacerbates antigen driven airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma

Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability

Changing the threshold—Signals and mechanisms of mast cell priming

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