Allergen-dependent solubilization of IL-13 receptor α2 reveals a novel mechanism to regulate allergy

Daines, Michael O.; Chen, Weiguo; Tabata, Yasuhiro; Walker, B; Gibson, Aaron M.; Masino, J.A.; Warrier, Manoj R.; Daines, Cori; Wenzel, Sally E.; Hershey, Gurjit K. Khurana

doi:10.1016/j.jaci.2006.09.039

Cited by 29 publications

(24 citation statements)

References 37 publications

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“…Human IL-13Rα2 was detected by ELISA, as previously described (31), modified only by the use of polyclonal goat anti-human IL-13Rα2 (1 μg/ml; R&D Systems, Minneapolis, MN) for the capture Ab. The standard curve was linear from 100–8000 pg/ml.…”

Section: Methodsmentioning

confidence: 99%

IL-13Rα2 Has a Protective Role in a Mouse Model of Cutaneous Inflammation

Sivaprasad¹,

Warrier

Gibson³

et al. 2010

The Journal of Immunology

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IL-13 is expressed in lesions of atopic dermatitis (AD) and has been associated with increased disease severity. IL-13 has two cognate receptors: IL-13Rα1 and IL-13Rα2. Although IL-13Rα2 expression is known to be induced in response to IL-13 in keratinocytes, its function in AD has never been evaluated. We characterized the loss of skin barrier function and the development of cutaneous inflammation in IL-13Rα2–null versus wild-type BALB/c mice following an epicutaneous allergen-sensitization/challenge model that shares similarities with human AD. Mice lacking IL-13Rα2 had significantly increased transepidermal water loss, cutaneous inflammation, peripheral eosinophilia, and IgG1 and IgE levels compared with wild-type mice. The rate of resolution of the cutaneous inflammation was not significantly altered in the IL-13Rα2–null mice. IL-13 induced expression of IL-13Rα2 in keratinocyte cell lines and primary human keratinocytes. Depletion of IL-13Rα2 in a keratinocyte cell line resulted in increased STAT6 signaling in response to IL-13. In conclusion, IL-13Rα2 serves a protective role in the pathogenesis of allergic inflammation and loss of skin barrier function in a mouse model of AD, suggesting that it may be an important endogenous regulator of IL-13–induced cutaneous inflammation in humans.

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Section: Methodsmentioning

confidence: 99%

IL-13Rα2 Has a Protective Role in a Mouse Model of Cutaneous Inflammation

Sivaprasad¹,

Warrier

Gibson³

et al. 2010

The Journal of Immunology

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“…Our results are consistent with those reported by Munitz et al [27] who demonstrated that mucus gene upregulation in a mouse model of allergic lung inflammation is dependent on IL-13Rα1. Further studies to investigate the role of IL-13Rα2 in allergic lung inflammation models driven by house dust mite, an aeroallergen shown to cleave IL-13Rα2 from the cell surface [28], and that stimulates robust fibrosis, angiogenesis and airways hyperreactivity in mice [29], are planned.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes

Berry

Adams

Airey

et al. 2009

International Immunopharmacology

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“…Matsumura et al [20] reported that endogenous MMP(s) [matrix metalloproteinase(s)] solubilize IL-13Rα2 in airway epithelial cells, whereas Chen et al [21] demonstrated that soluble IL-13Rα2 can be produced by means of direct cleavage by MMP-8 and that MMP-8 contributes to the solubilization of IL-13Rα2 in BALF (bronchoalveolar lavage fluid) in house dust mite-treated mice. Furthermore, this group showed that exposure to mould or house dust mite allergens resulted in degradation of surface IL-13Rα2 [22]. This reduction in receptor levels may contribute to the pathogenesis of allergic disorders in individuals with allergy because of the loss of IL-13Rα2 inhibition of IL-13 responses.…”

Section: Il-13rα2mentioning

confidence: 96%

Cytoplasmic tail of IL-13Rα2 regulates IL-4 signal transduction

Andrews

Nordgren

Kirby

et al. 2009

Biochemical Society Transactions

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IL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Ralpha1 (IL-13 receptor alpha-chain 1) and IL-4Ralpha. The second IL-13R (IL-13 receptor) has been identified, namely IL-13Ralpha2. This has been thought to be a decoy receptor due to its short cytoplasmic tail and its high binding affinity for IL-13 but not IL-4. IL-13Ralpha2 exists on the cell membrane, intracellularly and in a soluble form. Recent reports revealed that membrane IL-13Ralpha2 may have some signalling capabilities, and a soluble form of IL-13Ralpha2 can be generated in the presence of environmental allergens such as DerP. Interestingly, IL-13Ralpha2 has also been shown to regulate both IL-13 and IL-4 response in primary airway cells, despite the fact that IL-13Ralpha2 does not bind IL-4. The regulator mechanism is still unclear but the physical association of IL-13Ralpha2 with IL-4Ralpha appears to be a key regulatory step. These results suggest that the cytoplasmic tail of IL-13Ralpha2 may interfere with the association or activation of signalling molecules, such as JAK1 (Janus kinase 1), on IL-4Ralpha and thus prevents downstream signal cascade. The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2.

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Allergen-dependent solubilization of IL-13 receptor α2 reveals a novel mechanism to regulate allergy

Cited by 29 publications

References 37 publications

IL-13Rα2 Has a Protective Role in a Mouse Model of Cutaneous Inflammation

IL-13Rα2 Has a Protective Role in a Mouse Model of Cutaneous Inflammation

In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes

Cytoplasmic tail of IL-13Rα2 regulates IL-4 signal transduction

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