Dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) as regulators of T cell function and targets of immunotherapy in CNS inflammation

Reinhold, Dirk; Biton, Aliza; Pieper, Stefanie; Lendeckel, Uwe; Faust, Jürgen; Neubert, Klaus; Bank, Ute; Täger, Michael; Ansorge, Siegfried; Brocke, Stefan

doi:10.1016/j.intimp.2006.07.023

Cited by 49 publications

(49 citation statements)

References 28 publications

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“…In our study, we also showed down-regulation of SPARC-like1 in malignant thyroid tumors (Table 2). DPP4/CD26 is a homodimeric type II transmembrane glycoprotein and is identical to the leukocyte surface antigen CD26 (37). It is known to form a complex with seprase and thereby facilitate local degradation of extracellular matrices resulting in invasion of the endothelial cells into these matrices (38).…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Prasad¹,

Somervell²,

Tufano³

et al. 2008

Clinical Cancer Research

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Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as ''suspicious'' or ''indeterminate.'' Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription^PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription^PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.

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Section: Discussionmentioning

confidence: 99%

Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Prasad¹,

Somervell²,

Tufano³

et al. 2008

Clinical Cancer Research

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“…Apart from its enzymatic activity, its expression defines a T-helper (Th)1/Th0 phenotype among T cells and correlates with enhanced production of Th1-like cytokines. In addition, DPP IV/CD26 inhibitors have been shown to be effective in limiting immune activation processes and to modify the course of disease associated with an imbalanced T cell response, as in IBD (Bank et al , 2008Reinhold et al 2006;Yazbeck et al 2008).…”

mentioning

confidence: 99%

Development and resolution of colitis in mice with target deletion of dipeptidyl peptidase IV

Detel¹,

Pugel

Batičić³

et al. 2012

Experimental Physiology

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A role for dipeptidyl peptidase IV (DPP IV/CD26) in the pathogenesis of inflammatory bowel disease has been proposed owing to its involvement in immune regulation via its expression on immune cells and ability to cleave biologically active molecules. The aim of this study was to investigate the influence of DPP IV/CD26 deficiency on development and resolution of dextran sulfate sodium-induced colitis in CD26-deficient (CD26 −/− ) and wild-type (C57BL/6) mice. Colitis was characterized by clinical and histological changes and infiltration of immune cells in the colonic mucosa. In the acute phase of colitis, loss of body mass and disease activity in C57BL/6 mice was more intensive than in CD26 −/− mice, in spite of similar histopathological changes at the local level. Although acute inflammation induced a significant increase in the number of macrophages and dendritic cells in both mouse strains, in CD26 −/− mice the increase of macrophages was twice that in C57BL/6 animals (18.0 ± 4.5 versus 41.3 ± 5.8), whereas the increase in dendritic cells was more pronounced in C57BL/6 mice. In the acute phase of colitis, colonic DPP IV/CD26 activity was significantly decreased in C57BL/6 mice compared with healthy animals. The results of our study reveal that DPP IV/CD26 deficiency affects the onset of clinical symptoms and the specific cells infiltrating at the site of inflammation in CD26 −/− animals, suggesting a pathophysiological role of DPP IV/CD26 and providing new insights into the nature of the immune response activated during the development of colitis.

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“…CD13 is a cell membrane glycoprotein and also called Aminopeptidase N as it can hydrolyze amino acid from the end N of peptide, amide and aryl amide. It has been found that CD13 can regulate the activation of T lymphocytes, the proliferation and secretion of cytokines, and their inhibitors are of potential effect on psoriasis, skin keratosis abnormities and inflammatory diseases (Reinhold et al, 2006;Thielitz et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine regulatory role of Merkel cells in the pathogenesis of psoriasis

TaiHua¹,

Liu²,

Wang³

et al. 2011

Sci. Res. Essays

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It has been confirmed that neuroendocrine regulation involves in the pathogenesis of psoriasis, but the association between neuroendocrine and skin immune is still unknown. The present study aimed to explore the relationship of Merkel cells in the skin lesions and the pathogenesis of psoriasis. The ultrastructure of Merkel cells was observed under an electron microscope and immunohistochemistry was performed to detect the expressions of CK20, CK19, CK18, S100A7, SP and CD13 in the skin lesions of psoriasis patients and normal controls. Our results showed the neuroendocrine granules in the Merkel cells increased significantly at the progressive stage of psoriasis; the expressions of CK20, CK19 and CK18 in the skin lesions were markedly higher than those in normal controls, the CK20 expression at the progressive stage was significantly higher than that at the initial stage and recovery stage; the expressions of S100A7, SP and CD13 in the skin lesions at the progressive stage were higher than those in the initial stage and recovery stage and positively related to the CK20 expression. Merkel cells may play an important neuroendocrine regulatory role in the pathogenesis of psoriasis.

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Dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) as regulators of T cell function and targets of immunotherapy in CNS inflammation

Cited by 49 publications

References 28 publications

Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Development and resolution of colitis in mice with target deletion of dipeptidyl peptidase IV

Neuroendocrine regulatory role of Merkel cells in the pathogenesis of psoriasis

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