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Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12 production
Laura Conejero, … , Paola Brandi, David Sancho
Laura Conejero, … , Paola Brandi, David Sancho
Published May 18, 2017
Citation Information: JCI Insight. 2017;2(10):e90420. https://doi.org/10.1172/jci.insight.90420.
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Research Article Immunology Inflammation

Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12 production

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Abstract

DCs are necessary and sufficient for induction of allergic airway inflammation. CD11b+ DCs direct the underlying Th2 immunity, but debate surrounds the function of CD103+ DCs in lung immunity and asthma after an allergic challenge. We challenged Batf3–/– mice, which lacked lung CD103+ DCs, with the relevant allergen house dust mite (HDM) as a model to ascertain their role in asthma. We show that acute and chronic HDM exposure leads to defective Th1 immunity in Batf3-deficient mice. In addition, chronic HDM challenge in Batf3–/– mice results in increased Th2 and Th17 immune responses and exacerbated airway inflammation. Mechanistically, Batf3 absence does not affect induction of Treg or IL-10 production by lung CD4+ T cells following acute HDM challenge. Batf3-dependent CD103+ migratory DCs are the main source of IL-12p40 in the mediastinal lymph node DC compartment in the steady state. Moreover, CD103+ DCs selectively increase their IL-12p40 production upon HDM administration. In vivo IL-12 treatment reverts exacerbated allergic airway inflammation upon chronic HDM challenge in Batf3–/– mice, restraining Th2 and Th17 responses without triggering Th1 immunity. These results suggest a protective role for lung CD103+ DCs to HDM allergic airway inflammation through the production of IL-12.

Authors

Laura Conejero, Sofía C. Khouili, Sarai Martínez-Cano, Helena M. Izquierdo, Paola Brandi, David Sancho

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Figure 1

Batf3–/– mice lack CD103+ cDC1s in the lung and mLN and show a reduced CD8α+ cDC1 compartment in mLN.

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Batf3–/– mice lack CD103+ cDC1s in the lung and mLN and show a reduced ...
(A) HDM sensitization and challenge regime (acute protocol). (B) Gating strategy for lung Batf3-dependent DCs. (C) Staining of lung CD103+ and CD11b+ DCs in mice treated as indicated in A. Left: representative plots. Right: percentage of CD103+ cDC1s in the CD11c+MHCII+ compartment in the lung. (D) HDM administration protocol to evaluate early DC response following allergen challenge. (E) Gating strategy to identify migratory (mig) and resident (res) DCs in mLNs. (F and G) Res-DCs (F) and mig-DCs (G) in mLNs from mice i.n. challenged with 100 μg HDM. Left: representative plots. Right: percentage of Batf3-dependent DCs in the CD11c+MHCII+ compartment in the mLN. (C, F, and G) Individual data (n = 3–4 PBS, n = 6–7 HDM) and mean ± SEM of 1 representative experiment of 3 performed. *P < 0.05, ***P < 0.001, 1-way ANOVA followed by Bonferroni’s post-test. HDM, house dust mite; mLN, mediastinal lymph nodes.

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