鞘氨醇-1-磷酸受体4型在体内参与调节腹膜B-1细胞的贩运和分布。

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Janik Riese, Annabel Kleinwort, Maurice Hannemann, Celine Hähnel, Stephan Kersting, Tobias Schulze
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引用次数: 0

摘要

B-1 细胞在免疫防御、炎症调节和自身免疫方面发挥着至关重要的作用。B-1 细胞主要位于腹膜腔和胸膜腔,但在稳态条件下,体腔 B-1 细胞会在全身循环。趋化因子 CXCL12 和 CXCL13 已被确定为腹膜 B 细胞迁移的主要调节因子。在缺乏鞘氨醇-1-磷酸受体 4(S1PR4)的小鼠中,腹腔中的 B-1a 和 B-1b 细胞数量会减少,其机制不明。在这项研究中,我们发现 S1PR4 介导的 S1P 信号在体外改变了腹膜 B 细胞对 CXCL13 和 CXCL12 的趋化反应。在体内,S1PR4 介导的 S1P 信号既影响向腹腔的迁移,也影响从腹腔的移出。用wt或s1pr4 -/-腹膜B细胞对scid小鼠进行的长期重组实验显示,腹膜B细胞在次级淋巴器官中有不同的分布模式。作为一种功能性结果,在使用 s1pr4 -/- 腹膜细胞重组的小鼠中,B-1a 细胞的主要产物--浆液和粘膜 IgM 水平都降低了。总之,我们的数据确定 S1PR4 是第二个 S1P 受体(除 S1PR1 外),它在调控腹膜 B-1 细胞功能方面发挥着关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sphingosine-1-phosphate receptor type 4 is critically involved in the regulation of peritoneal B-1 cell trafficking and distribution in vivo

Sphingosine-1-phosphate receptor type 4 is critically involved in the regulation of peritoneal B-1 cell trafficking and distribution in vivo

B-1 cells are crucially involved in immune defense and regulation of inflammation and autoimmunity. B-1 cells are predominantly located in the peritoneal and pleural cavities, although body cavity B-1 cells recirculate systemically under steady-state conditions. The chemokines CXCL12 and CXCL13 have been identified as the main regulators of peritoneal B-cell trafficking. In mice deficient for sphingosine-1-phosphate receptor 4 (S1PR4), B-1a and B-1b cell numbers are reduced in the peritoneal cavity by an unknown mechanism. In this study, we show that S1PR4-mediated S1P signaling modifies the chemotactic response of peritoneal B cells to CXCL13 and CXCL12 in vitro. In vivo, S1PR4-mediated S1P signaling affects both immigration into and emigration from the peritoneal cavity. Long-term reconstitution experiments of scid mice with wt or s1pr4–/– peritoneal B cells revealed a distinct distributional pattern in secondary lymphoid organs. As a functional consequence, both plasmatic and mucosal IgM levels, the main product of B-1a cells, are reduced in mice reconstituted with s1pr4–/– peritoneal cells. In summary, our data identify S1PR4 as the second S1P receptor (besides S1PR1), which is critically involved in the regulation of peritoneal B-1 cell function.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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