Lineage extrinsic and intrinsic control of immunoregulatory cell numbers by SHIP.
Lineage extrinsic and intrinsic control of immunoregulatory cell numbers by SHIP.
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DOI：
10.1002/eji.201142092
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发表时间：
2012-07
影响因子：
5.4
通讯作者：
Kerr, William G.
中科院分区：
文献类型：
--
作者：
Collazo, Michelle M.;Paraiso, Kim H. T.;Park, Mi-Young;Hazen, Amy L.;Kerr, William G.
我们以前发现，生殖系或诱导的SHIP缺陷可以扩大T淋巴系和髓系系中的免疫调节细胞数量。我们推测，这些增长可能是相互关联的。在这里，我们显示髓系特异性消融SHIP导致髓系来源的抑制细胞(MDSC)和调节性T细胞(Treg)数量的扩张，这表明髓系细胞类型对Treg数量的依赖控制。相反，T系特异性消融舰船导致Treg数的扩张，但不导致MDSC间隔的扩张，这表明Ship也具有限制Treg数的谱系内在作用。然而，促进MDSC和Treg扩张的SHIP缺陷髓系细胞不是MDSC，因为它们缺乏SHIP蛋白表达。因此，体内MDSC数量的调节必须由另一种髓系细胞以细胞外的方式控制。我们之前已经证明，在SHIP−/−小鼠中，G-csf水平显著增加，这表明这种骨髓细胞生长因子可能以一种外在的方式促进骨髓间充质干细胞的扩张。与这一假设一致，我们发现，成年后船体缺陷的小鼠的MDSC脾间室扩张需要G-CSF。因此，SHIP部分通过限制骨髓细胞生长因子G-CSF的产生来控制MDSC的数量。
We previously showed that germline or induced SHIP-deficiency expands immunoregulatory cell numbers in T lymphoid and myeloid lineages. We postulated these increases could be interrelated. Here we show that myeloid specific ablation of SHIP leads to expansion of both myeloid-derived suppressor cell (MDSC) and regulatory T cell (Treg) numbers indicating SHIP-dependent control of Treg numbers by a myeloid cell type. Conversely, T lineage specific ablation of SHIP leads to expansion of Treg numbers, but not expansion of the MDSC compartment, indicating SHIP also has a lineage intrinsic role in limiting Treg numbers. However, the SHIP-deficient myeloid cell that promotes MDSC and Treg expansion is not an MDSC as they lack SHIP protein expression. Thus, regulation of MDSC numbers in vivo must be controlled in a cell extrinsic fashion by another myeloid cell type. We had previously shown that G-CSF levels are profoundly increased in SHIP−/− mice suggesting this myelopoietic growth factor could promote MDSC expansion in a cell extrinsic fashion. Consistent with this hypothesis, we find that G-CSF is required for expansion of the MDSC splenic compartment in mice rendered SHIP-deficient as adults. Thus, SHIP controls MDSC numbers, in part, by limiting production of the myelopoietic growth factor G-CSF.
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影响因子：
20.3
作者：
Hazen, Amy L.;Smith, Michelle J.;Kerr, William G.
通讯作者：
Kerr, William G.
影响因子：
11.4
作者：
Huber, M;Helgason, CD;Krystal, G
通讯作者：
Krystal, G
影响因子：
4.4
作者：
Kuroda, Etsushi;Ho, Victor;Krystal, Gerald
通讯作者：
Krystal, Gerald
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
4.4
作者：
Brooks, Robert;Fuhler, Gwenny M.;Kerr, William G.
通讯作者：
Kerr, William G.