17 research outputs found

    Arginase 1+ IL-10+ polymorphonuclear myeloid-derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

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    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells, which are characterized by their capability to suppress T-cell responses. While MDSCs have been traditionally associated with cancer diseases, their role as regulators of autoimmune diseases is emerging. Pemphigus is a chronic autoimmune blistering skin disease characterized by dysregulated T-cell responses and autoantibody production. The role of MDSCs in pemphigus disease has not been defined yet. The aim of this study was to characterize MDSCs in pemphigus patients and to dissect their relationship with CD4(+) T-cell subsets and clinical disease assessments. For this purpose, we performed a cross-sectional analysis of 20 patients with pemphigus. Our results indicate that a population of CD66b(+)CD11b(+) polymorphonuclear-like MDSCs (PMN-MDSCs) is expanded in the peripheral blood mononuclear cell fraction of pemphigus patients compared to age-matched healthy donors. These PMN-MDSCs have the capability of suppressing allogeneic T-cell proliferation in vitro and show increased expression of characteristic effector molecules such as arginase I and interleukin-10. We further demonstrate that PMN-MDSCs are especially expanded in patients with active pemphigus, but not in patients in remission. Moreover, MDSC frequencies correlate with an increased Th2/Th1 cell ratio. In conclusion, the identification of a functional PMN-MDSC population suggests a possible role of these cells as regulators of Th cell responses in pemphigus

    CXCR4 +

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    Pseudomonas aeruginosa airway infection recruits and modulates neutrophilic myeloid-derived suppressor cells

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    Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF) lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK)-cell responses. Here we demonstrate, using an airway in vivo infection model, that P. aeruginosa recruits and activates neutrophilic MDSCs, which functionally suppress T-cell responses. We further show that the CF gene defect (cystic fibrosis transmembrane conductance regulator, CFTR) modulates the functionality, but not the recruitment or generation of neutrophilic MDSCs. Collectively, we define a mechanism by which P. aeruginosa airway infection undermines host immunity by modulating neutrophilic MDSCs in vivo

    Inflammatory cells in BALF and lung tissue.

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    <p>(A) Mice were treated according to the injection schedule for the HDM-induced asthma model. (B) BALF was centrifuged and cells were analyzed via differential cell count. Differences remained non-significant. Data are presented as mean ± SEM; n = 3. (C) Representative micrographs of BALF cellspin preparations are shown (scale 100 μm, magnification x200). (D) Levels of neutrophils and eosinophils in lung tissue were measured via flow cytometry. Differences remained non-significant. Data are presented as mean ± SEM; n = 3.</p

    Groups of mice and their respective treatment following the injection schedule of Fig 1A.

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    <p>Groups of mice and their respective treatment following the injection schedule of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154001#pone.0154001.g001" target="_blank">Fig 1A</a>.</p
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