Reduced airway inflammation in CD26/DPP4-deficient F344 rats is associated with altered recruitment patterns of regulatory T cells and expression of pulmonary surfactant proteins

• Published in: Clinical and experimental allergy Vol. 40; no. 12; pp. 1794 - 1808
• Main Authors: Schmiedl, A., Krainski, J., Schwichtenhövel, F., Schade, J., Klemann, C., Raber, K. A., Zscheppang, K., Beekmann, T., Acevedo, C., Glaab, T., Wedekind, D., Pabst, R., Von Hörsten, S., Stephan, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2010; Blackwell; Wiley Subscription Services, Inc
• Subjects: Animal models; Animals; asthma; Asthma - genetics; Asthma - immunology; Asthma - pathology; Biological and medical sciences; CD26; CD26 antigen; Chronic obstructive pulmonary disease, asthma; Dipeptidyl Peptidase 4 - genetics; Disease Models, Animal; Epithelial cells; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunoregulation; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Lung; Lung - immunology; Lung - pathology; Lymphocytes T; Medical sciences; OVA; Ovalbumin; Pneumology; Pulmonary Surfactant-Associated Proteins - metabolism; Rats; Rats, Inbred F344; Respiratory tract diseases; surfactant; Surfactants; T-Lymphocytes, Regulatory - immunology; Tregs; Rat; Respiratory system; Recruitment; Respiratory tract; Association; Immunology; Pulmonary surfactant; T-Lymphocyte; Bronchus disease; Obstructive pulmonary disease; Regulatory cell; surfactant; Lung disease; Respiratory disease; Deficiency; Tregs; Rodentia; Inflammation; Protein; Asthma; Vertebrata; Mammalia; Animal; CD26; OVA
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2010.03547.x

Summary
Introduction
CD26 is highly expressed on lung epithelial cells as well as on immune cells. Ovalbumin (OVA)‐induced airway inflammation induces a further increase of CD26 expression. CD26‐deficient rat strains exhibit blunted clinical courses in models of experimental asthma.
Objective
(1) To investigate the involvement of regulatory T cells (Tregs) and the surfactant system in a rat model of genetic CD26 deficiency. (2) To investigate regulatory mechanisms dependent on the endogenous CD26 expression. (3) To investigate the impact of CD26 on surfactant protein (SP)‐levels under inflammatory conditions.
Methods
Wild‐type and CD26‐deficient F344 rats were sensitized to and challenged with OVA. Subsequently, airway inflammation, SP levels as well as surface tension of the bronchoalveolar lavage (BAL) fluid were evaluated.
Results
CD26 deficiency led to decreased airway inflammation, e.g. reduced numbers of eosinophils and activated T cells in the BAL. Remarkably, the CD26‐deficient rats exhibited a significantly increased influx of FoxP3+ Tregs into the lungs and increased IL‐10‐secretion/production by draining lymph node cells in culture experiments. Furthermore, in OVA‐challenged CD26‐deficient rats, the increase of the expression of the collectins SP‐A and SP‐D as well as of the surface tension‐active SP‐B was significantly less pronounced than in the CD26‐positive strain. Only in the wild‐type rats, functional alterations of the surfactant system, e.g. the increased surface tension were obvious after OVA challenge.
Conclusion
Reduced airway inflammation in CD26‐deficient F344 rats appear to be mediated by differences in the recruitment and activity of Tregs. This altered inflammation is associated with differences in the SP expression as well as function.
Cite this as: A. Schmiedl, J. Krainski, F. Schwichtenhövel, J. Schade, C. Klemann, K. A. Raber, K. Zscheppang, T. Beekmann, C. Acevedo, T. Glaab, D. Wedekind, R. Pabst, S. von Hörsten and M. Stephan, Clinical & Experimental Allergy, 2010 (40) 1794–1808.