TY  - JOUR
A1  - Ruck, Tobias
A1  - Bittner, Stefan
A1  - Afzali, Ali Maisam
A1  - Göbel, Kerstin
A1  - Glumm, Sarah
A1  - Kraft, Peter
A1  - Sommer, Claudia
A1  - Kleinschnitz, Christoph
A1  - Preusse, Corinna
A1  - Stenzel, Werner
A1  - Wiendl, Heinz
A1  - Meuth, Sven G.
T1  - The NKG2D-IL-15 signaling pathway contributes to T-cell mediated pathology in inflammatory myopathies
JF  - Oncotarget
N2  - NKG2D is an activating receptor on T cells, which has been implicated in the pathogenesis of autoimmune diseases. T cells are critically involved in idiopathic inflammatory myopathies (IIM) and have been proposed as specific therapeutic targets. However, the mechanisms underlying T cell-mediated progressive muscle destruction in IIM remain to be elucidated. We here determined the involvement of the NKG2D - IL-15 signaling pathway. Primary human myoblasts expressed NKG2D ligands, which were further upregulated upon inflammatory stimuli. In parallel, shedding of the soluble NKG2D ligand MICA (sMICA) decreased upon inflammation potentially diminishing inhibition of NKG2D signaling. Membrane-related expression of IL-15 by myoblasts induced differentiation of naive CD8\(^+\) T cells into highly activated, cytotoxic \(CD8^+NKG2D^{high}\) T cells demonstrating NKG2D-dependent lysis of myoblasts in vitro. \(CD8^+NKG2D^{high}\) T cell frequencies were increased in the peripheral blood of polymyositis (PM) patients and correlated with serum creatinine kinase concentrations, while serum sMICA levels were not significantly changed. In muscle biopsy specimens from PM patients expression of the NKG2D ligand MICA/B was upregulated, IL-15 was expressed by muscle cells, CD68\(^+\) macrophages as well as CD4\(^+\) T cells, and \(CD8^+NKG2D^+\) cells were frequently detected within inflammatory infiltrates arguing for a local signaling circuit in the inflammatory muscle milieu. In conclusion, the NKG2D - IL-15 signaling pathway contributes to progressive muscle destruction in IIM potentially opening new therapeutic avenues.
KW  - MIC ligands
KW  - pathology section
KW  - T cell activation
KW  - idiopathic inflammatory myopathies
KW  - polymyositis
KW  - IL-15
KW  - NKG2D
KW  - receptor
KW  - expression
KW  - lymphokine-activated killer
KW  - human muscle-cells
KW  - multiple sclerosis
KW  - celiac disease
KW  - tumor immunity
KW  - NKG2D ligands
KW  - cutting edge
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136047
VL  - 6
IS  - 41
ER  - 
TY  - JOUR
A1  - Ickrath, Pascal
A1  - Sprügel, Lisa
A1  - Beyersdorf, Niklas
A1  - Scherzad, Agmal
A1  - Hagen, Rudolf
A1  - Hackenberg, Stephan
T1  - Detection of Candida albicans-Specific CD4+ and CD8+ T Cells in the Blood and Nasal Mucosa of Patients with Chronic Rhinosinusitis
JF  - Journal of Fungi
N2  - Candida albicans is ubiquitously present, and colonization in the nose and oral cavity is common. In healthy patients, it usually does not act as a pathogen, but in some cases can cause diseases. The influence of C. albicans as a trigger of T cell activation on the pathogenesis of chronic rhinosinusitis (CRS) is controversial, and its exact role is not clear to date. The aim of the present study was to detect and characterize C. albicans-specific CD4+ and CD8+ T cells in patients with CRS, with and without nasal polyps. Tissue and blood samples were collected from patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP), and from healthy controls. A peptide pool derived from C. albicans antigen was added to tissue and blood samples. After 6 days, lymphocytes were analyzed by multicolor flow cytometry. Activation was assessed by the intracellular marker Ki-67, and the cytokine secretion was measured. Tissue CD8+ T cells of CRSsNP patients showed a significantly higher proportion of Ki-67+ cells after activation with C. albicans antigen compared to peripheral blood CD8+ T cells. Cytokine secretion in response to C. albicans antigen was similar for all study groups. In this study, C. albicans-specific CD4+ and CD8+ T cells were detected in peripheral blood and mucosal tissue in all study groups. In patients suffering from CRSsNP, C. albicans-specific CD8+ T cells were relatively enriched in the nasal mucosa, suggesting that they might play a role in the pathogenesis of CRSsNP.
KW  - Candida albicans
KW  - chronic rhinosinusitis
KW  - T cell activation
KW  - nasal polyps
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239671
SN  - 2309-608X
VL  - 7
IS  - 6
ER  -