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CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis.

Authors: Agostini, C  Calabrese, F  Poletti, V  Marcer, G  Facco, M  Miorin, M  Cabrelle, A  Baesso, I  Zambello, R  Trentin, L  Semenzato, G 
Citation: Agostini C, etal., Respir Res. 2005 Feb 22;6:20.
Pubmed: (View Article at PubMed) PMID:15725351
DOI: Full-text: DOI:10.1186/1465-9921-6-20

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined. METHODS: Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung. RESULTS: Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+)/IFNgamma(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-gamma, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP. CONCLUSION: These data indicate that IFN-gamma mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation.

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CRRD Object Information
CRRD ID: 5135490
Created: 2011-07-22
Species: All species
Last Modified: 2011-07-22
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.