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Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10.

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Title: Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10.
Authors: Meng, Lingzhang, Almeida, Larissa Nogueira, Clauder, Ann-Katrin, Lindemann, Timo, Luther, Julia, Link, Christopher, Hofmann, Katharina, Kulkarni, Upasana, Wong, David Ming, David, Jean-Pierre, Manz, Rudolf Armin
Source: Frontiers in Immunology; 5/31/2019, pN.PAG-N.PAG, 13p
Subject Terms: MYELOID differentiation factor 88, BONE marrow, CELL differentiation, INTERLEUKIN-10, LABORATORY mice
Abstract: Bone marrow plasma cells have been reported to represent a major source of IL-10; however, the impact of plasma cell derived IL-10 in that tissue remains poorly understood. We confirm in this study that even in the absence of acute immune reactions, mature plasma cells represent the dominant IL-10+ cell population in the bone marrow, and identify myeloid-lineage cells as a main local target for plasma cell derived IL-10. Using Vert-X IL-10 transcriptional reporter mice, we found that more than 50% of all IL-10+ cells in bone marrow were CD138+ plasma cells, while other IL-10+ B lineage cells were nearly absent in this organ. Accordingly, IL-10 was found in the supernatants of short-term cultures of FACS-sorted bone marrow plasma cells, confirming IL-10 secretion from these cells. IL-10+ bone marrow plasma cells showed a B220−/CD19−/MHCII low phenotype suggesting that these cells represent a mature differentiation stage. Approximately 5% of bone marrow leucocytes expressed the IL-10 receptor (IL-10R), most of them being CD115+/Ly6C+/CD11c− monocytes. Compared to littermate controls, young B lineage specific IL-10 KO mice showed increased numbers of CD115+ cells but normal populations of other myeloid cell types in bone marrow. However, at 7 months of age B lineage specific IL-10 KO mice exhibited increased populations of CD115+ myeloid and CD11c+ dendritic cells (DCs), and showed reduced F4/80 expression in this tissue; hence, indicating that bone marrow plasma cells modulate the differentiation of local myeloid lineage cells via IL-10, and that this effect increases with age. The effects of B cell/plasma cell derived IL-10 on the differentiation of CD115+, CD11c+, and F4/80+ myeloid cells were confirmed in co-culture experiments. Together, these data support the idea that IL-10 production is not limited to early plasma cell stages in peripheral tissues but is also an important feature of mature plasma cells in the bone marrow. Moreover, we provide evidence that already under homeostatic conditions in the absence of acute immune reactions, bone marrow plasma cells represent a non-redundant source for IL-10 that modulates local myeloid lineage differentiation. This is particularly relevant in older individuals. [ABSTRACT FROM AUTHOR]
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10.
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  Data: <searchLink fieldCode="AR" term="%22Meng%2C+Lingzhang%22">Meng, Lingzhang</searchLink><br /><searchLink fieldCode="AR" term="%22Almeida%2C+Larissa+Nogueira%22">Almeida, Larissa Nogueira</searchLink><br /><searchLink fieldCode="AR" term="%22Clauder%2C+Ann-Katrin%22">Clauder, Ann-Katrin</searchLink><br /><searchLink fieldCode="AR" term="%22Lindemann%2C+Timo%22">Lindemann, Timo</searchLink><br /><searchLink fieldCode="AR" term="%22Luther%2C+Julia%22">Luther, Julia</searchLink><br /><searchLink fieldCode="AR" term="%22Link%2C+Christopher%22">Link, Christopher</searchLink><br /><searchLink fieldCode="AR" term="%22Hofmann%2C+Katharina%22">Hofmann, Katharina</searchLink><br /><searchLink fieldCode="AR" term="%22Kulkarni%2C+Upasana%22">Kulkarni, Upasana</searchLink><br /><searchLink fieldCode="AR" term="%22Wong%2C+David+Ming%22">Wong, David Ming</searchLink><br /><searchLink fieldCode="AR" term="%22David%2C+Jean-Pierre%22">David, Jean-Pierre</searchLink><br /><searchLink fieldCode="AR" term="%22Manz%2C+Rudolf+Armin%22">Manz, Rudolf Armin</searchLink>
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  Data: Frontiers in Immunology; 5/31/2019, pN.PAG-N.PAG, 13p
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  Data: <searchLink fieldCode="DE" term="%22MYELOID+differentiation+factor+88%22">MYELOID differentiation factor 88</searchLink><br /><searchLink fieldCode="DE" term="%22BONE+marrow%22">BONE marrow</searchLink><br /><searchLink fieldCode="DE" term="%22CELL+differentiation%22">CELL differentiation</searchLink><br /><searchLink fieldCode="DE" term="%22INTERLEUKIN-10%22">INTERLEUKIN-10</searchLink><br /><searchLink fieldCode="DE" term="%22LABORATORY+mice%22">LABORATORY mice</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Bone marrow plasma cells have been reported to represent a major source of IL-10; however, the impact of plasma cell derived IL-10 in that tissue remains poorly understood. We confirm in this study that even in the absence of acute immune reactions, mature plasma cells represent the dominant IL-10+ cell population in the bone marrow, and identify myeloid-lineage cells as a main local target for plasma cell derived IL-10. Using Vert-X IL-10 transcriptional reporter mice, we found that more than 50% of all IL-10+ cells in bone marrow were CD138+ plasma cells, while other IL-10+ B lineage cells were nearly absent in this organ. Accordingly, IL-10 was found in the supernatants of short-term cultures of FACS-sorted bone marrow plasma cells, confirming IL-10 secretion from these cells. IL-10+ bone marrow plasma cells showed a B220−/CD19−/MHCII low phenotype suggesting that these cells represent a mature differentiation stage. Approximately 5% of bone marrow leucocytes expressed the IL-10 receptor (IL-10R), most of them being CD115+/Ly6C+/CD11c− monocytes. Compared to littermate controls, young B lineage specific IL-10 KO mice showed increased numbers of CD115+ cells but normal populations of other myeloid cell types in bone marrow. However, at 7 months of age B lineage specific IL-10 KO mice exhibited increased populations of CD115+ myeloid and CD11c+ dendritic cells (DCs), and showed reduced F4/80 expression in this tissue; hence, indicating that bone marrow plasma cells modulate the differentiation of local myeloid lineage cells via IL-10, and that this effect increases with age. The effects of B cell/plasma cell derived IL-10 on the differentiation of CD115+, CD11c+, and F4/80+ myeloid cells were confirmed in co-culture experiments. Together, these data support the idea that IL-10 production is not limited to early plasma cell stages in peripheral tissues but is also an important feature of mature plasma cells in the bone marrow. Moreover, we provide evidence that already under homeostatic conditions in the absence of acute immune reactions, bone marrow plasma cells represent a non-redundant source for IL-10 that modulates local myeloid lineage differentiation. This is particularly relevant in older individuals. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3389/fimmu.2019.01183
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        Text: English
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        PageCount: 13
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      – SubjectFull: MYELOID differentiation factor 88
        Type: general
      – SubjectFull: BONE marrow
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      – SubjectFull: CELL differentiation
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      – SubjectFull: INTERLEUKIN-10
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              Text: 5/31/2019
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