Interleukin-13: Central Mediator of Allergic Asthma

Wills‐Karp, Marsha; Luyimbazi, Jackie; Xu, Xueying; Schofield, Brian; Neben, Tamlyn Y.; Karp, Christopher; Donaldson, Debra D.

doi:10.1126/science.282.5397.2258

Cited by 2,487 publications

(2,045 citation statements)

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“…IL-13, a Th2-type cytokine, is a central mediator for allergic inflammation [8,9]. The blockade of IL-13 markedly inhibits allergen-induced airway hyperresponsiveness, mucus production, and eosinophilia whereas IL-13 delivery to the airway causes these effects in mice [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…The blockade of IL-13 markedly inhibits allergen-induced airway hyperresponsiveness, mucus production, and eosinophilia whereas IL-13 delivery to the airway causes these effects in mice [8][9][10][11]. Therefore, IL-13 as well as TSLP is necessary and sufficient for the development of allergic inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…these effects in mice [8][9][10][11]. Therefore, IL-13 as well as TSLP is necessary and sufficient for the development of allergic inflammation.…”

mentioning

confidence: 98%

“…Endogenous stimulators of TSLP production might be released upon the cellular damage associated with the tissue isolation and contribute to the basal TSLP production. This issue is presently under investigation.IL-13 plays a central role in the development of airway inflammation in asthma and allergic rhinitis [8][9][10][11][22][23][24]. Recent studies suggested that TSLP functions upstream of IL-13 in the skin and lung allergic inflammation [12,13].…”

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Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

et al. 2009

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Both thymic stromal lymphopoietin (TSLP) and IL-13 are essential cytokines for the development of allergic inflammation. However, a causal link between TSLP and IL- 13 has not yet been fully elucidated. This study aimed to investigate whether IL-13 induces TSLP expression and whether the induction contributes to the development of allergic inflammation. We found that IL-13 induced TSLP expression in mouse nasal tissue specimens in a Stat6-dependent manner. In addition, intranasal challenge of mice with IL-13 induced TSLP expression in the nasal epithelium. Importantly, intranasal IL-13 challenge induced eosinophilia and goblet cell hyperplasia in the nasal mucosa in mice, which was inhibited by the blockade of TSLP activity with anti-TSLP Ab. These findings suggest that TSLP is an important mediator of IL-13-driven allergic inflammation in the nasal mucosa. Taken together with the recent findings that IL-13 is a critical downstream element for TSLP-driven allergic inflammation, TSLP may function both upstream and downstream of IL-13, thus providing an additional rationale as to why TSLP plays such a central role in the development of allergic inflammation.Key words: Allergic inflammation . Epithelial cells . IL-13 . Thymic stromal lymphopoietin Supporting Information available online IntroductionThymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which binds to a TSLP receptor (TSLPR) consisting of the IL-7 receptor a-chain and a common g receptor-like chain [1,2]. TSLP was originally identified as a factor derived from a thymic stromal cell line that could support the growth of a mouse B-cell line [3].However, recent evidence has demonstrated TSLP, derived from epithelial cells, to be a critical factor for allergic inflammation [1,2,4]. For instance, transgenic mice expressing TSLP in keratinocytes or in lung epithelial cells develop atopic dermatitisor asthma-like inflammation in the skin or the lung, respectively, while TSLPR-deficient mice fail to develop an inflammatory lung response to inhaled antigen [5][6][7].IL-13, a Th2-type cytokine, is a central mediator for allergic inflammation [8,9]. The blockade of IL-13 markedly inhibits allergen-induced airway hyperresponsiveness, mucus production, and eosinophilia whereas IL-13 delivery to the airway causes SHORT COMMUNICATION 3078these effects in mice [8][9][10][11]. Therefore, IL-13 as well as TSLP is necessary and sufficient for the development of allergic inflammation. However, the relationship between TSLP and IL-13 in allergic inflammation has not yet been fully elucidated.This study thus investigated the causal link between IL-13 and TSLP in allergic inflammation. For this purpose, we examined the effects of IL-13 on TSLP expression both in vitro and in vivo using mouse nasal tissue explants and a mouse model of allergic inflammation in the nasal mucosa, respectively. The current results suggest that TSLP is induced by IL-13 and is critical for the development of IL-13-driven allergic inflammation. Because recent studies suggest that TSLP-dri...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…these effects in mice [8][9][10][11]. Therefore, IL-13 as well as TSLP is necessary and sufficient for the development of allergic inflammation.…”

mentioning

confidence: 98%

mentioning

confidence: 99%

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Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

et al. 2009

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“…Th2‐type cytokines such as interleukin (IL)‐4, IL‐5 and IL‐13 stimulate the production of allergen‐specific immunoglobulin (Ig) E in B cells and infiltration of eosinophils into the lungs. This results in the release of various substances, such as histamine, leukotriene and prostaglandin D 2 , through degranulation of mast cells, causing mucus production and bronchoconstriction 3, 4, 5, 6. Thus, many studies have developed antibodies for the treatment or prevention of allergic asthma by targeting Th2 immune pathophysiological factors 7, 8, 9, 10.…”

Section: Introductionmentioning

confidence: 99%

DW2008S and its major constituents from Justicia procumbens exert anti‐asthmatic effect via multitargeting activity

Youm

Lee

Choi

et al. 2018

J Cellular Molecular Medi

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Our previous study revealed that the ethanolic extract of Justicia procumbens ameliorates ovalbumin‐induced airway inflammation and airway hyper‐responsiveness in a mouse model of asthma. However, the mechanism of action of the extract remains unknown. In this study, we prepared DW2008S, an optimized and standardized powder extracted from J. procumbens using anhydrous ethanol, and investigated its anti‐asthmatic effect and mechanism of action. Our results showed that DW2008S contains two major ingredients, justicidin A (JA) and justicidin B (JB), which selectively inhibit T helper 2 (Th2) cell responses in concanavalin A‐activated spleen cells and polarized Th2 cells. Blockade of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine‐based inhibition motif domains (TIGIT) using a neutralizing antibody also selectively inhibited Th2 cell responses. Furthermore, DW2008S regulated TIGIT expression in the mice and cultured cells. Additionally, DW2008S and JA antagonized human adenosine receptor A3 (A3 AR), which mediates mast cell‐dependent inflammation and bronchoconstriction. DW2008S and JB inhibited human phosphodiesterase 4 (PDE4), which is known to cause bronchoconstriction; however, the required concentrations were higher than those needed to affect TIGIT . These findings suggest that DW2008S can potentially ameliorate Th2‐driven airway inflammation and bronchoconstriction through negative regulation of TIGIT and blockade of A3 AR and PDE4 activities.

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Characterization in mice of the immunological properties of five allergenic acid anhydrides

Dearman

Warbrick

Humphreys

et al. 2000

J of Applied Toxicology

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Occupational exposure to certain acid anhydrides, including trimellitic anhydride (TMA), maleic anhydride (MA), phthalic anhydride (PA), hexahydrophthalic anhydride (HHPA) and methyltetrahydrophthalic anhydride (MTHPA), has been associated with the development of respiratory allergy or asthma. There is considerable debate about the mechanisms through which such chemicals may cause respiratory sensitization, particularly concerning a universal requirement for specific IgE antibody. Despite the controversy regarding an obligatory role for IgE, there is a growing consensus that chemical respiratory hypersensitivity is associated with the selective development of T lymphocytes with a type 2 (Th2) phenotype. In the current investigations we have characterized in mice the nature of immune responses provoked by prolonged topical exposure to five acid anhydrides. Under application conditions where similar overall immunogenicity was achieved, we have compared cytokine responses induced by PA, MA, HHPA and MTHPA with those provoked by concurrent exposure to TMA or to the reference contact allergen 2, 4-dinitrochlorobenzene (DNCB). Lymph node cells (LNC) draining the site of topical exposure to DNCB invariably expressed high levels of the type 1 cytokines interferon-gamma (IFN-gamma) and interleukin-12 (IL-12), but only low levels of the type 2 cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10). In each experiment, TMA-activated LNC displayed the converse, type 2, phenotype of cytokine production. The other acid anhydrides in each case provoked a type 2 cytokine secretion profile, with comparable IL-10 expression but somewhat less vigorous IL-4 production compared with that observed following exposure to the reference respiratory allergen TMA. In every experiment relatively low levels of IFN-gamma and IL-12 were elaborated by acid anhydride-activated LNC, with the exception of PA-stimulated LNC that displayed increased amounts of IL-12 in comparison with other acid anhydrides. Thus, prolonged topical exposure of mice to five different acid anhydrides in each case resulted in the development of a predominantly Th2-type cytokine secretion phenotype, consistent with the ability of these materials to provoke asthma and respiratory allergy through a type 2 (possibly IgE-mediated) mechanism. Taken together with the results of previous investigations with a wider range of chemical allergens, these data suggest that induced cytokine secretion patterns or 'fingerprints' allow discrimination between contact and respiratory allergens and consequently represent a suitable approach to prospective evaluation of respiratory sensitization hazard.

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Interleukin-13: Central Mediator of Allergic Asthma

Cited by 2,487 publications

References 40 publications

Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

DW2008S and its major constituents from Justicia procumbens exert anti‐asthmatic effect via multitargeting activity

Characterization in mice of the immunological properties of five allergenic acid anhydrides

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