Intrinsic functional defects of type 2 innate lymphoid cells impair innate allergic inflammation in promyelocytic leukemia zinc finger (PLZF)–deficient mice - 05/02/16
Abstract |
Background |
The transcription factor promyelocytic leukemia zinc finger (PLZF) is transiently expressed during development of type 2 innate lymphoid cells (ILC2s) but is not present at the mature stage. We hypothesized that PLZF-deficient ILC2s have functional defects in the innate allergic response and represent a tool for studying innate immunity in a mouse with a functional adaptive immune response.
Objective |
We determined the consequences of PLZF deficiency on ILC2 function in response to innate and adaptive immune stimuli by using PLZF−/− mice and mixed wild-type:PLZF−/− bone marrow chimeras.
Methods |
PLZF−/− mice, wild-type littermates, or mixed bone marrow chimeras were treated with the protease allergen papain or the cytokines IL-25 and IL-33 or infected with the helminth Nippostrongylus brasiliensis to induce innate type 2 allergic responses. Mice were sensitized with intraperitoneal ovalbumin-alum, followed by intranasal challenge with ovalbumin alone, to induce adaptive TH2 responses. Lungs were analyzed for immune cell subsets, and alveolar lavage fluid was analyzed for ILC2-derived cytokines. In addition, ILC2s were stimulated ex vivo for their capacity to release type 2 cytokines.
Results |
PLZF-deficient lung ILC2s exhibit a cell-intrinsic defect in the secretion of IL-5 and IL-13 in response to innate stimuli, resulting in defective recruitment of eosinophils and goblet cell hyperplasia. In contrast, the adaptive allergic inflammatory response to ovalbumin and alum was unimpaired.
Conclusions |
PLZF expression at the innate lymphoid cell precursor stage has a long-range effect on the functional properties of mature ILC2s and highlights the importance of these cells for innate allergic responses in otherwise immunocompetent mice.
Le texte complet de cet article est disponible en PDF.Key words : Allergic mechanisms, innate lymphoid cells, mouse models
Abbreviations used : CLP, DAPI, ICOS, ILC, ILC2, IL-7Rα, iNKT, KO, PLZF, PMA, Rag, TCR, WT
Plan
| Supported by National Institutes of Health grants T32 HL007605 (to P.A.V.) and R01HL118092, R01AI038339, and AI108643 (A.B.) and the University of Chicago Digestive Research Core Center Grant P30DK42086. |
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| Disclosure of potential conflict of interest: P. A. Verhoef and A. Bendelac have received research support from the National Institutes of Health (NIH; RO1 HL118092, RO1 AI038339, and P30DK42086) and are employed by the University of Chicago. M. G. Constantinides has received research support from the NIH (RO1 HL118092, RO1 AI038339, and R01AI108643). B. D. McDonald has received research support from the NIH (RO1 HL118092, RO1 AI038339, and P30DK42086). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 2
P. 591 - février 2016 Retour au numéro
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