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2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties

OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood...

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Autores principales: Florez-Pollack, Stephanie, Tseng, Lin-chiang, Kobayashi, Masato, Chong, Benjamin F., Ariizumi, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799011/
http://dx.doi.org/10.1017/cts.2018.57
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author Florez-Pollack, Stephanie
Tseng, Lin-chiang
Kobayashi, Masato
Chong, Benjamin F.
Ariizumi, Kiyoshi
author_facet Florez-Pollack, Stephanie
Tseng, Lin-chiang
Kobayashi, Masato
Chong, Benjamin F.
Ariizumi, Kiyoshi
author_sort Florez-Pollack, Stephanie
collection PubMed
description OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood of DLE patients and evaluate their ability to suppress autologous T cells. METHODS/STUDY POPULATION: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 32 CLE patients and 16 age-matched and gender-matched controls were analyzed using flow cytometry. Monocytic MDSCs were identified by the phenotype of CD14+ HLA-DR neg/low. Furthermore, autologous MDSCs and T cells were purified from CLE PBMCs (n=4) and co-cultured at different ratios of these cells. T cell function was measured by secretion of IFN-γ by ELISA. RESULTS/ANTICIPATED RESULTS: Monocytic MDSCs in CLE PBMCs (median: 2.04%, IQR: 0.67%–5.07%) were significantly higher compared with healthy control PBMCs (median: 0.5%, IQR: 0.1%–1.07%, p=0.002). Although not significant on subset analysis, patients with CLE limited to the head and neck had the highest levels of MDSCs. CLE MDSCs (n=4) were found to suppress autologous activated T-cells in a dose-dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: In this cross-sectional study of patients of the UT Southwestern Cutaneous Lupus Registry, we observed differences in the levels of MDSCs among PBMCs of CLE patients Versus healthy controls. CLE patients had significantly higher levels of MDSCs, which could be explained by the presence of an inflammatory state in this group. Furthermore, CLE MDSCs were able to suppress autologous T cells, showing that these cells are functionally patent in CLE blood. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity.
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spelling pubmed-67990112019-10-28 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties Florez-Pollack, Stephanie Tseng, Lin-chiang Kobayashi, Masato Chong, Benjamin F. Ariizumi, Kiyoshi J Clin Transl Sci Basic/Translational Science/Team Science OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood of DLE patients and evaluate their ability to suppress autologous T cells. METHODS/STUDY POPULATION: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 32 CLE patients and 16 age-matched and gender-matched controls were analyzed using flow cytometry. Monocytic MDSCs were identified by the phenotype of CD14+ HLA-DR neg/low. Furthermore, autologous MDSCs and T cells were purified from CLE PBMCs (n=4) and co-cultured at different ratios of these cells. T cell function was measured by secretion of IFN-γ by ELISA. RESULTS/ANTICIPATED RESULTS: Monocytic MDSCs in CLE PBMCs (median: 2.04%, IQR: 0.67%–5.07%) were significantly higher compared with healthy control PBMCs (median: 0.5%, IQR: 0.1%–1.07%, p=0.002). Although not significant on subset analysis, patients with CLE limited to the head and neck had the highest levels of MDSCs. CLE MDSCs (n=4) were found to suppress autologous activated T-cells in a dose-dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: In this cross-sectional study of patients of the UT Southwestern Cutaneous Lupus Registry, we observed differences in the levels of MDSCs among PBMCs of CLE patients Versus healthy controls. CLE patients had significantly higher levels of MDSCs, which could be explained by the presence of an inflammatory state in this group. Furthermore, CLE MDSCs were able to suppress autologous T cells, showing that these cells are functionally patent in CLE blood. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity. Cambridge University Press 2018-11-21 /pmc/articles/PMC6799011/ http://dx.doi.org/10.1017/cts.2018.57 Text en © The Association for Clinical and Translational Science 2018 http://creativecommons.org/licenses/by/4.0/ This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic/Translational Science/Team Science
Florez-Pollack, Stephanie
Tseng, Lin-chiang
Kobayashi, Masato
Chong, Benjamin F.
Ariizumi, Kiyoshi
2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
title 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
title_full 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
title_fullStr 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
title_full_unstemmed 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
title_short 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
title_sort 2456 cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
topic Basic/Translational Science/Team Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799011/
http://dx.doi.org/10.1017/cts.2018.57
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