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J Allergy Clin Immunol. 2012 Jan;129(1):191-8.e1-4. doi: 10.1016/j.jaci.2011.09.041. Epub 2011 Nov 12.

Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity.

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  • 1MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

Abstract

BACKGROUND:

IL-4, IL-5, and IL-13 are thought to be central to the allergic asthmatic response. Previous work supposed that the essential source of these cytokines was CD4(+) T(H)2 cells. However, more recent studies have suggested that other innate production of type 2 cytokines might be as important.

OBJECTIVES:

Nuocytes are a novel population of IL-13-producing innate cells, which are critical for protective immunity in Nippostrongylus brasiliensis infection. Given this, we investigated the potential existence and functional importance of nuocytes in experimental allergic asthma.

METHODS:

We generated Il4(+/eGFP)Il13(+/Tomato) dual-reporter mice to study cytokine-producing cells during allergic inflammation. We adoptively transferred innate IL-13-producing cells to investigate their role in airways hyperreactivity (AHR).

RESULTS:

We show that allergen-induced nuocytes infiltrate the lung and are a major innate source of IL-13. CD4(+) T cells in the lung almost exclusively express only IL-13, whereas IL-4-producing T cells were restricted to the draining lymph nodes. Intranasal administration of IL-25 or IL-33 induced IL-13-producing nuocytes in the BAL fluid. Strikingly, adoptive transfer of wild-type nuocytes, but not Il13(-/-) nuocytes, into Il13(-/-) mice, which are normally resistant to IL-25-induced AHR, restored airways resistance and lung cell infiltration.

CONCLUSIONS:

These findings identify nuocytes as a novel cell type in allergic lung inflammation and an innate source of IL-13 that can directly induce AHR in the absence of IL-13-producing CD4(+) T cells. These data highlight nuocytes as an important new consideration in the development of future allergic asthma therapy.

PMID:
22079492
DOI:
10.1016/j.jaci.2011.09.041
[PubMed - indexed for MEDLINE]
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