Hypersensitivity pneumonitis onset and severity is regulated by CD103 dendritic cell expression.

TitleHypersensitivity pneumonitis onset and severity is regulated by CD103 dendritic cell expression.
Publication TypeJournal Article
Year of Publication2017
AuthorsBernatchez, E, Langlois, A, Brassard, J, Flamand, N, Marsolais, D, Blanchet, M-R
JournalPLoS One
Date Published2017
KeywordsAlveolitis, Extrinsic Allergic, Animals, Antigens, Bacterial, Antigens, CD, Bronchoalveolar Lavage Fluid, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, Dendritic Cells, Disease Models, Animal, Down-Regulation, Immunoglobulin G, Integrin alpha Chains, Leukocytes, Lung, Mice, Mice, Knockout, Saccharopolyspora, Severity of Illness Index, Spleen, Th17 Cells

BACKGROUND: Pulmonary dendritic cells drive lung responses to foreign antigens, including Saccharopolyspora rectivirgula, a causative agent of hypersensitivity pneumonitis. While the airway inflammatory mechanisms involved in hypersensitivity pneumonitis are well described, the mechanisms leading to the break in homeostasis and hypersensitivity pneumonitis onset are not well-described, and could involve CD103+ dendritic cells, which are found at baseline and during inflammatory responses in the lung. However, recent demonstration of the ability of CD103+ dendritic cells to induce inflammatory responses starkly contrasts with their classically described role as regulatory cells. These discrepancies may be attributable to the lack of current information on the importance of CD103 expression and modulation on these cells during inflammatory episodes.METHODS: To verify the importance of CD103 expression in the regulation of hypersensitivity pneumonitis, wild-type and Cd103-/- mice were exposed intranasally to S. rectivirgula and airway inflammation was quantified. Surface expression of CD103 in response to S. rectivirgula exposure was studied and cell transfers were used to determine the relative importance of CD103 expression on dendritic cells and T cells in regulating the inflammation in hypersensitivity pneumonitis.RESULTS: Cd103-/- mice developed an exacerbated inflammatory response as early as 18h following S. rectivirgula exposure. CD103 expression on dendritic cells was downregulated quickly following S. rectivirgula exposure, and cell transfers demonstrated that CD103 expression on dendritic cells specifically (and not T cells) regulates the onset and severity of this response.CONCLUSION: All in all, we demonstrate that CD103 expression by dendritic cells, but not T cells, is crucial for homeostasis maintenance and the regulation of the TH17 airway inflammatory response in hypersensitivity pneumonitis.

Alternate JournalPLoS ONE
PubMed ID28628641
PubMed Central IDPMC5476273