Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity - 24/12/11
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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+ TH2 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+/eGFPIl13+/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.
Le texte complet de cet article est disponible en PDF.Key words : Nuocytes, IL-13, asthma, IL-25, IL-33
Abbreviations used : AHR, BAL, ICOS, IL-4eGFP, IL-13Tom, OVA, PE, rm, T1/ST2
Plan
J.L.B. and S.H.W. were supported by a grant from Centocor, and A.N.J.M. was supported by grants from the American Asthma Federation (no. 10-0078) and Asthma UK (no. 07/001). |
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Disclosure of potential conflict of interest: J. L. Barlow has received research support from Centocor. A. N. J. McKenzie has received research support from Centocor and the American Asthma Foundation. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 1
P. 191 - janvier 2012 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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