Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10
Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10
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DOI：
10.3389/fimmu.2019.01183
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发表时间：
2019-05-31
影响因子：
7.3
通讯作者：
Manz, Rudolf Armin
中科院分区：
文献类型：
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作者：
Meng, Lingzhang;Almeida, Larissa Nogueira;Manz, Rudolf Armin
据报道，骨髓浆细胞代表IL-10的主要来源;然而，浆细胞衍生的IL-10在该组织中的影响仍然知之甚少。我们在这项研究中证实，即使在没有急性免疫反应的情况下，成熟浆细胞也代表了骨髓中占主导地位的IL-10+细胞群，并将髓系细胞鉴定为浆细胞衍生的IL-10的主要局部靶标。使用Vert-X IL-10转录报告小鼠，我们发现骨髓中超过50%的所有IL-10+细胞是CD 138+浆细胞，而其他IL-10+ B谱系细胞在该器官中几乎不存在。因此，在FACS分选的骨髓浆细胞的短期培养物的上清液中发现了IL-10，证实了IL-10从这些细胞分泌。IL-10+骨髓浆细胞显示B220-/CD 19-/MHCII低表型，表明这些细胞代表成熟分化阶段。大约5%的骨髓白细胞表达IL-10受体（IL-10 R），其中大多数是CD 115 +/Ly 6C +/CD 11 c-单核细胞。与同窝对照组相比，年轻的B谱系特异性IL-10 KO小鼠显示出骨髓中CD 115+细胞数量增加，但其他髓样细胞类型的群体正常。然而，在7月龄时，B谱系特异性IL-10 KO小鼠表现出增加的CD 115+髓样和CD 11 c+树突状细胞（DC）群体，并且在该组织中表现出减少的F4/80表达;因此，表明骨髓浆细胞通过IL-10调节局部髓样谱系细胞的分化，并且这种作用随着年龄的增加而增加。在共培养实验中证实了源自B细胞/浆细胞的IL-10对CD 115+、CD 11 c+和F4/80+骨髓细胞分化的作用。总之，这些数据支持IL-10的产生不仅限于外周组织中的早期浆细胞阶段，而且也是骨髓中成熟浆细胞的重要特征。此外，我们提供的证据表明，在缺乏急性免疫反应的稳态条件下，骨髓浆细胞已经代表了调节局部髓系分化的IL-10的非冗余来源。这在老年人中尤其重要。
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.