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Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen

Nature Immunology volume 2, pages 725–731 (2001)Cite this article

Abstract

Respiratory exposure to allergen induces T cell tolerance and protection against the development of airway hyperreactivity and asthma. However, the specific mechanisms by which tolerance is induced by respiratory allergen are not clear. We report here that pulmonary dendritic cells (DCs) from mice exposed to respiratory antigen transiently produced interleukin 10 (IL-10). These phenotypically mature pulmonary DCs, which were B-7hi as well as producing IL-10, stimulated the development of CD4+ T regulatory 1–like cells that also produced high amounts of IL-10. In addition, adoptive transfer of pulmonary DCs from IL-10+/+, but not IL-10−/−, mice exposed to respiratory antigen induced antigen-specific unresponsiveness in recipient mice. These studies show that IL-10 production by DCs is critical for the induction of tolerance, and that phenotypically mature pulmonary DCs mediate tolerance induced by respiratory exposure to antigen.

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Figure 1: Administration of i.n. OVA induces T cell unresponsiveness and expression of T cell activation antigens.
Figure 2: Capacity and kinetics of antigen presentation by pulmonary DCs from mice exposed to i.n. OVA.
Figure 3: Phenotypic analysis of DCs from mice exposed to i.n. OVA.
Figure 4: Expression and kinetics of IL-10 in pulmonary DCs.
Figure 5: DCs from IL-10+/+, but not IL-10−/−, mice exposed to i.n. OVA transfer T cell tolerance.
Figure 6: Stimulation of T cells with pulmonary versus mesendric DCs.

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Acknowledgements

Supported by the NIH Public Health Service (RO1HL62348, AI24571 and AI26322) and the California Lung Association.

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  1. Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, Stanford University, Stanford, 94305-5208, CA, USA

    Omid Akbari, Rosemarie H. DeKruyff & Dale T. Umetsu

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Correspondence to Dale T. Umetsu.

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Akbari, O., DeKruyff, R. & Umetsu, D. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2, 725–731 (2001). https://doi.org/10.1038/90667

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