Influence of CD26/dipeptidyl peptidase IV deficiency on immunophenotypic changes during colitis development and resolution

Abstract

A lot of evidence for the importance of CD26/dipeptidyl peptidase IV (CD26/DPP IV) in immunoactivation has been reported; however, its involvement in colitis remains unclear. The aim of this study was to investigate the influence of CD26/DPP IV deficiency on immunophenotypic changes associated with dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) and CD26-deficient mice. Development of clinical symptoms of colitis and animal health status parameters were assessed; the expression of the nuclear factor (NF)-κB p65 subunit was measured by quantitative real-time PCR, while cell characterization was determined by flow cytometry and immunohistochemical staining. DSS treatment induced loss of body weight and colon length shortening in both mouse strains. An increase of myeloperoxidase activity in CD26-deficient mice was more intensive than in WT mice, in spite of similar histopathological changes. Furthermore, a significant increase in the expression of NF-κB p65 subunit in the colon of CD26-deficient mice was determined. The percentage of splenic CD4+ and CD8+ cells in the acute phase of colitis was significantly decreased in WT mice, while in the same period, an increase in the percentage of splenic CD8+ cells was present in CD26-deficient mice. Development of colitis was accompanied by a significant increase in the percentage of intrahepatic NKT cells in both mouse strains, but their percentage in spleen was increased only in CD26-deficient mice. CD26 deficiency was associated with a heightened response to DSS accompanied by increased expression of NF-κB p65 subunit and distinct changes in leukocyte trafficking. These results provide new insights into the role of CD26/DPP IV during the development of colitis.

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Acknowledgments

The research was supported by the Ministry of Science, Education and Sports of the Republic of Croatia, grant no. 062-0061245-0213 and University of Rijeka, grant no. 13.06.1.2.26. We gratefully acknowledge Professor Didier Marguet (Centre d’Immunologie de Marseille-Luiny, Université de la Méditerrance, Marseille, France), for providing CD26-deficient animals. The authors wish to thank Ioannis Pateras, MD, PhD (Department of Histology, National and Kapodistrian University of Athens, Greece) for performing p65 immunohistochemical staining, as well as the head of the Department Professor Vassilis Gorgoulis, for his affability. We kindly thank Professor Siniša Volarević (Department of Molecular Biology, School of Medicine, University of Rijeka, Croatia) for continuous support and collaboration through the TransMedRi project and Professor Stipan Jonjić for allowing us to use all the facilities of the Department of Histology and Embryology, School of Medicine, University of Rijeka, Croatia. The authors would like to thank Tihana and Ben Harrison for valuable language suggestions.

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Correspondence to Dijana Detel.

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Detel, D., Buljevic, S., Pucar, L.B. et al. Influence of CD26/dipeptidyl peptidase IV deficiency on immunophenotypic changes during colitis development and resolution. J Physiol Biochem 72, 405–419 (2016). https://doi.org/10.1007/s13105-016-0491-7

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Keywords

  • Inflammatory bowel disease
  • CD26/dipeptidyl peptidase IV
  • CD26-deficient animals
  • Dextran sulfate sodium
  • Immune response