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J Immunol. 2019 Jun 10. pii: ji1900113. doi: 10.4049/jimmunol.1900113. [Epub ahead of print]

A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.

Author information

1
Department of Medicine, Pulmonary and Critical Care, Baylor College of Medicine, Houston, TX 77030.
2
Section of Diabetes and Endocrinology, Department of Pediatrics, McNair Medical Institute, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030.
3
Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, TX 77030.
4
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030; and.
5
Biology of Inflammation Center, Baylor College of Medicine, Houston, TX 77030.
6
Section of Diabetes and Endocrinology, Department of Pediatrics, McNair Medical Institute, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030; farrahk@bcm.edu Maria.Bettini@bcm.edu.
7
Department of Medicine, Pulmonary and Critical Care, Baylor College of Medicine, Houston, TX 77030; farrahk@bcm.edu Maria.Bettini@bcm.edu.

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+ 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.

PMID:
31182478
DOI:
10.4049/jimmunol.1900113

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