Increased hematopoietic cells in the mertk-/- mouse peritoneal cavity: a result of augmented migration.
Increased hematopoietic cells in the mertk-/- mouse peritoneal cavity: a result of augmented migration.
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DOI：
10.4049/jimmunol.0902784
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Matsushima GK
中科院分区：
文献类型：
--
作者：
Williams JC;Wagner NJ;Earp HS;Vilen BJ;Matsushima GK
腹膜腔被认为是自身反应性B细胞转运到其他免疫组织之前的重要部位;然而，对可能调控这一过程的基因知之甚少。缺乏受体酪氨酸激酶Mertk的小鼠表现出狼疮样自身免疫表型，伴有脾肿大和高自身抗体滴度。在这里，我们研究Mertk是否调节有利于自身免疫表型的腹膜细胞的组成。我们发现，与野生型小鼠相比，mertk−/−小鼠腹腔中巨噬细胞、DC、浆细胞样DC、T细胞和B细胞的数量增加。细胞数量的这种差异不是由于细胞增殖或细胞死亡的变化。在过继转移实验中，我们发现标记的供体细胞迁移到mertk−/−腹膜腔的增加。此外，骨髓嵌合小鼠显示造血衍生因子对T细胞迁移也至关重要。与这种迁移和细胞数量的增加相一致，我们确定了mertk−/−小鼠腹膜细胞上CXCL 9及其受体CXCR 3和IL-7受体的表达升高。为了证实CXCR 3对细胞的迁移功能，CXCR 3供体细胞的耗竭显著减少了进入mertk−/−小鼠腹膜的过继转移细胞的数量。腹膜细胞数量的这种控制与自身抗体产生相关，并且完全归因于Mertk，因为缺乏其他家族成员Axl或Tyro 3的小鼠未显示腹膜细胞数量或自身免疫表型的失调。
The peritoneal cavity is recognized as an important site for autoreactive B cells prior to their transit to other immune tissues; however, little is known of the genes that may regulate this process. Mice lacking the receptor tyrosine kinase Mertk display a lupus-like autoimmune phenotype with splenomegaly and high autoantibodies titers. Here, we investigate whether Mertk regulates the composition of peritoneal cells that favor an autoimmune phenotype. We found an increase in the number of macrophages, DC, plasmacytoid DC, T cells and B cells in the peritoneal cavity of mertk−/− mice when compared to wild-type mice. This disparity in cell numbers was not due to changes in cell proliferation or cell death. In adoptive transfer experiments, we showed an increase in migration of labeled donor cells into the mertk−/− peritoneal cavity. In addition, bone marrow chimeric mice showed hematopoietic-derived factors were also critical for T cell migration. Consistent with this migration and the increase in the number of cells, we identified elevated expression of CXCL9, its receptor CXCR3, and IL-7 receptor on peritoneal cells from mertk−/− mice. To corroborate the migratory function of CXCR3 on cells, the depletion of CXCR3 donor cells significantly reduced the number of adoptively transferred cells that entered into the peritoneum of mertk−/− mice. This control of peritoneal cells numbers correlated with autoantibody production and was exclusively attributed to Mertk since mice lacking other family members, Axl or Tyro 3, did not display dysregulation in peritoneal cell numbers or the autoimmune phenotype.
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DOI：
10.1084/jem.157.1.202
发表时间：
1983-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hayakawa K;Hardy RR;Parks DR;Herzenberg LA
通讯作者：
Herzenberg LA
影响因子：
5.4
作者：
Behrens, EM;Gadue, P;Cohen, PL
通讯作者：
Cohen, PL
影响因子：
4.4
作者：
MURAKAMI, M;YOSHIOKA, H;HONJO, T
通讯作者：
HONJO, T
影响因子：
4.4
作者：
Uehara, Hiroshi;Shacter, Emily
通讯作者：
Shacter, Emily
影响因子：
3.5
作者：
Gohlke PR;Williams JC;Vilen BJ;Dillon SR;Tisch R;Matsushima GK
通讯作者：
Matsushima GK