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      Cells´ Flow and Immune Cell Priming under alternating g-forces in Parabolic Flight

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          Abstract

          Gravitational stress in general and microgravity (µg) in particular are regarded as major stress factors responsible for immune system dysfunction in space. To assess the effects of alternating µg and hypergravity (hyper-g) on immune cells, the attachment of peripheral blood mononuclear cells (PBMCs) to adhesion molecules under flow conditions and the antigen-induced immune activation in whole blood were investigated in parabolic flight (PF). In contrast to hyper-g (1.8 g) and control conditions (1 g), flow and rolling speed of PBMCs were moderately accelerated during µg-periods which were accompanied by a clear reduction in rolling rate. Whole blood analyses revealed a “primed” state of monocytes after PF with potentiated antigen-induced pro-inflammatory cytokine responses. At the same time, concentrations of anti-inflammatory cytokines were increased and monocytes displayed a surface molecule pattern that indicated immunosuppression. The results suggest an immunologic counterbalance to avoid disproportionate immune responses. Understanding the interrelation of immune system impairing and enhancing effects under different gravitational conditions may support the design of countermeasures to mitigate immune deficiencies in space.

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          Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease

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            Non-Classical monocytes display inflammatory features: Validation in Sepsis and Systemic Lupus Erythematous

            Given the importance of monocytes in pathogenesis of infectious and other inflammatory disorders, delineating functional and phenotypic characterization of monocyte subsets has emerged as a critical requirement. Although human monocytes have been subdivided into three different populations based on surface expression of CD14 and CD16, published reports suffer from contradictions with respect to subset phenotypes and function. This has been attributed to discrepancies in reliable gating strategies for flow cytometric characterization and purification protocols contributing to significant changes in receptor expression. By using a combination of multicolour flow cytometry and a high-dimensional automated clustering algorithm to confirm robustness of gating strategy and analysis of ex-vivo activation of whole blood with LPS we demonstrate the following: a. ‘Classical’ monocytes are phagocytic with no inflammatory attributes, b. ‘Non-classical’ subtype display ‘inflammatory’ characteristics on activation and display properties for antigen presentation and c. ‘Intermediate’ subtype that constitutes a very small percentage in circulation (under physiological conditions) appear to be transitional monocytes that display both phagocytic and inflammatory function. Analysis of blood from patients with Sepsis, a pathogen driven acute inflammatory disease and Systemic Lupus Erythmatosus (SLE), a chronic inflammatory disorder validated the broad conclusions drawn in the study.
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              The HLA System: Genetics, Immunology, Clinical Testing, and Clinical Implications

              The human major histocompatibility complex HLA is located on the short arm of chromosome 6. It is known to be the most polymorphic genetic system in humans. The biological role of the HLA class I and class II molecules is to present processed peptide antigens. The HLA system is clinically important as transplantation antigens. Molecular HLA allele typing is routinely performed to provide HLA class I and class II allele matching in unrelated donor hematopoietic stem cell transplantation. Prospective lymphocyte crossmatching is critical in solid organ transplantation to prevent allograft rejection. HLA alloimmunization causes various problems in transfusion therapy. The HLA system is associated with certain diseases, but its underlying mechanisms are not yet fully explained.
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                Author and article information

                Contributors
                mlong@imech.ac.cn
                alexander.chouker@med.uni-muenchen.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                2 August 2019
                2 August 2019
                2019
                : 9
                : 11276
                Affiliations
                [1 ]Laboratory of Translational Research “Stress and Immunity”, Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany
                [2 ]GRID grid.458484.1, Key Laboratory of Microgravity (National Microgravity Laboratory), Center of Biomechanics and Bioengineering, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, , Institute of Mechanics, Chinese Academy of Sciences, ; Beijing, 100190 China
                [3 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, School of Engineering Sciences, , University of Chinese Academy of Sciences, ; Beijing, 100049 China
                [4 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Institute of Anatomy, Faculty of Medicine, , University of Zurich, ; Zurich, Switzerland
                [5 ]ISNI 0000 0001 1018 4307, GRID grid.5807.a, Department of Machine Design, Engineering Design and Product Development (IMK), , Otto-von-Guericke-University Magdeburg, ; Magdeburg, Germany
                Author information
                http://orcid.org/0000-0002-3156-2976
                Article
                47655
                10.1038/s41598-019-47655-x
                6677797
                31375732
                8637205a-a3b9-4a0c-b119-1d9c3df33f17
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 December 2018
                : 4 July 2019
                Funding
                Funded by: German Space Agency (DLR) on behalf of the Federal Ministry of Economics and Technology, Grant number 50WB1622
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: U1738115 and 31661143044
                Award ID: U1738115 and 31661143044
                Award ID: U1738115 and 31661143044
                Award ID: U1738115 and 31661143044
                Award ID: U1738115 and 31661143044
                Award Recipient :
                Funded by: Chinese Academy of Sciences (XDA0402020219, XDA04020416, XDA04073800, and QYZDJSSW-JSC018XDA15014100)
                Funded by: German Space Agency (DLR), Grant number: 50WB1519
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                inflammation,innate immunity
                Uncategorized
                inflammation, innate immunity

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