Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFκB-inducing kinase in stromal cells
Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFκB-inducing kinase in stromal cells
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DOI：
10.1182/blood-2007-10-120071
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发表时间：
2008-05-01
期刊：
影响因子：
20.3
通讯作者：
Kiyono, Hiroshi
中科院分区：
文献类型：
--
作者：
Kunisawa, Jun;Gohda, Masashi;Kiyono, Hiroshi
我们以前报道过1-磷酸鞘氨醇（S1 P）调节腹膜B细胞运输和随后的肠道伊加产生，但其潜在机制仍然不清楚。我们在这里证明，核因子κ B诱导激酶（NIK）参与调节S1 P介导的腹膜B细胞的运输。尽管来自NIK突变的发育不全（aly）小鼠的腹膜B细胞表达1型S1 P受体（S1 P（1））的水平相当，并表现出向S1 P的正常迁移，但aly腹膜B细胞对FTY 720（一种S1 P（1）调节剂）的敏感性降低。NIK突变的基质细胞显示粘附分子（VCAM-1和ICAM-1）水平降低，CXCL 13表达增加，导致支持S1 P介导的腹膜B细胞迁移的能力受损，而不是迁移。因此，aly腹膜B细胞表现出正常的S1 P介导的腹膜B细胞运输从腹膜到肠伊加的生产时，他们被转移到严重的联合免疫缺陷或野生型小鼠。然而，S1 P介导的野生型B细胞从aly腹膜腔的迁移受损，而不影响其从血液中的迁移。此外，野生型基质细胞转移到腹膜恢复S1 P介导的腹膜B细胞的运输。这些发现表明，基质细胞中的INK在调节S1 P介导的腹膜B细胞的运输中具有特定的作用。
We previously reported that sphingosine 1-phosphate (S1P) regulates peritoneal B-cell trafficking and subsequent intestinal IgA production, but the underlying mechanisms remain obscure. We demonstrate here that nuclear factor kappa B-inducing kinase (NIK) is involved in the regulation of S1P-mediated trafficking of peritoneal B cells. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed type 1 S1P receptor (S1P(1)) at comparable levels and demonstrated normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P(1) modulator. NIK-mutated stromal cells showed decreased levels of adhesion molecules (VCAM-1 and ICAM-1) and increased CXCL13 expressions, leading to impaired ability to support S1P-mediated emigration, but not immigration, of peritoneal B cells. Therefore, aly peritoneal B cells exhibited normal S1P-mediated peritoneal B-cell trafficking from peritoneum to intestine for IgA production when they were transferred into severe combined immunodeficient or wild-type mice. However, S1P-mediated emigration of wild-type B cells from the aly peritoneal cavity was impaired without affecting their immigration from the blood. Further, transfer of wild-type stromal cells into the peritoneum restored S1P-mediated trafficking of aly peritoneal B cells. These findings suggest that INK in stromal cells has a specific role in the regulation of S1P-mediated trafficking of peritoneal B cells.