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A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jul 15; Vol. 203 (2), pp. 349-359. Date of Electronic Publication: 2019 Jun 10. - Publication Year :
- 2019
-
Abstract
- Loss of immune tolerance to self-antigens can promote chronic inflammation and disrupt the normal function of multiple organs, including the lungs. Degradation of elastin, a highly insoluble protein and a significant component of the lung structural matrix, generates proinflammatory molecules. Elastin fragments (EFs) have been detected in the serum of smokers with emphysema, and elastin-specific T cells have also been detected in the peripheral blood of smokers with emphysema. However, an animal model that could recapitulate T cell-specific autoimmune responses by initiating and sustaining inflammation in the lungs is lacking. In this study, we report an animal model of autoimmune emphysema mediated by the loss of tolerance to elastin. Mice immunized with a combination of human EFs plus rat EFs but not mouse EFs showed increased infiltration of innate and adaptive immune cells to the lungs and developed emphysema. We cloned and expanded mouse elastin-specific CD4 <superscript>+</superscript> T cells from the lung and spleen of immunized mice. Finally, we identified TCR sequences from the autoreactive T cell clones, suggesting possible pathogenic TCRs that can cause loss of immune tolerance against elastin. This new autoimmune model of emphysema provides a useful tool to examine the immunological factors that promote loss of immune tolerance to self.<br /> (Copyright © 2019 by The American Association of Immunologists, Inc.)
- Subjects :
- Adaptive Immunity immunology
Animals
Cell Line
Disease Models, Animal
Female
HEK293 Cells
Humans
Immune Tolerance immunology
Immunity, Innate immunology
Inflammation immunology
Mice
Mice, Inbred C57BL
Pulmonary Disease, Chronic Obstructive immunology
Smoking immunology
Autoimmunity immunology
Elastin immunology
Lung immunology
Pulmonary Emphysema immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 203
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 31182478
- Full Text :
- https://doi.org/10.4049/jimmunol.1900113