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Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not been possible to track the sites and timing of antigen uptake or subsequent antigen presentation to effector T cells. In this study, we use two-photon microscopy of the lung parenchyma and note accumulation of CD11b(+) dendritic cells (DCs) around the airway after allergen challenge but very limited access of these airway-adjacent DCs to the contents of the airspace. In contrast, we observed prevalent transepithelial uptake of particulate antigens by alveolar DCs. These distinct sites are temporally linked, as early antigen uptake in alveoli gives rise to DC and antigen retention in the airway-adjacent region. Antigen-specific T cells also accumulate in the airway-adjacent region after allergen challenge and are activated by the accumulated DCs. Thus, we propose that later airway hyperreactivity results from selective retention of allergen-presenting DCs and antigen-specific T cells in airway-adjacent interaction zones, not from variation in the abilities of individual DCs to survey the lung.

Original publication

DOI

10.1084/jem.20112667

Type

Journal article

Journal

The Journal of experimental medicine

Publication Date

06/2012

Volume

209

Pages

1183 - 1199

Addresses

Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.

Keywords

Lung, Pulmonary Alveoli, Dendritic Cells, T-Lymphocytes, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Asthma, Bronchial Hyperreactivity, Antigens, CD11c, Antigens, Allergens, Microscopy, Antigen Presentation, In Vitro Techniques