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

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

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 emergin...

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Bibliographic Details
Published in:Experimental dermatology Vol. 30; no. 6; pp. 782 - 791
Main Authors: Neri, Davide, Carevic‐Neri, Melanie, Brück, Jürgen, Holstein, Julia, Schäfer, Iris, Solimani, Farzan, Handgretinger, Rupert, Hartl, Dominik, Ghoreschi, Kamran
Format: Journal Article
Language:English
Published: Denmark Wiley Subscription Services, Inc 01-06-2021
Subjects:
Arginase
Autoantibodies
Autoimmune diseases
autoimmune skin blistering disease
autoimmunity
CD11b antigen
CD4 antigen
Cell proliferation
desmoglein
Disease
Lymphocytes T
MDSC
Myeloid cells
Pemphigus
Peripheral blood
Remission
Skin diseases
Suppressor cells
T helper cells
T helper cells
MDSC
autoimmunity
autoimmune skin blistering disease
desmoglein
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Summary: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.
Bibliography:Funding information
This work was supported by the PATE Fortüne Program of the university of Tübingen (project number 2540‐0‐0) to DN, by the fellowship of the Fondazione Benedetta è la Vita ONLUS to DN and by grants of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG); FOR 2497/TP02 (GH133/2‐1) to KG
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ISSN:0906-6705
1600-0625
DOI:10.1111/exd.14298