Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow.
Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow.
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DOI：
10.4049/jimmunol.1102242
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Pease LR
中科院分区：
文献类型：
--
作者：
Brickshawana A;Shapiro VS;Kita H;Pease LR
IL-33促进2型免疫应答，包括保护性和致病性。最近，IL-33的靶点，包括几种新发现的2型先天性细胞，已经在外周中被表征。在这项研究中，我们报告了野生型C57 BL/6小鼠的骨髓细胞与IL-33一起培养时产生IL-5和IL-13。来自Rag 1 KO和KitW-sh/W-sh小鼠的骨髓细胞的IL-33培养物也有相似的反应;因此，排除了T、B和肥大细胞的可能贡献。相反，细胞内染色显示IL-5和IL-13阳性细胞显示出与谱系−Sca-1+c-Kit− CD 25+（LSK− CD 25+）细胞一致的标记物特征，这是一种先前未知功能的骨髓细胞群。新鲜分离的LSK− CD 25+细胞均匀表达IL-33受体ST 2。此外，分选的LSK− CD 25+细胞的培养表明，当与IL-33加IL-2和IL-33加IL-7一起培养时，它们确实产生IL-5和IL-13。此外，向小鼠腹腔注射IL-33或IL-25诱导LSK− CD 25+细胞在大小和频率上扩增，并上调ST 2和α4β7整联蛋白（一种粘膜归巢标记物）。因此，我们在体外和体内鉴定了神秘的骨髓LSK− CD 25+细胞作为IL-33应答细胞，其属性与外周组织中描述的其他2型先天性细胞相似。
IL-33 promotes type 2 immune responses, both protective and pathogenic. Recently, targets of IL-33, including several newly discovered type 2 innate cells, have been characterized in the periphery. In this study, we report that bone marrow cells from wild-type C57BL/6 mice responded with IL-5 and IL-13 production when cultured with IL-33. IL-33 cultures of bone marrow cells from Rag1 KO and KitW-sh/W-sh mice also responded similarly; hence, eliminating the possible contributions of T, B, and mast cells. Rather, intracellular staining revealed that the IL-5– and IL-13–positive cells display a marker profile consistent with the Lineage−Sca-1+c-Kit−CD25+ (LSK−CD25+) cells, a bone marrow cell population of previously unknown function. Freshly isolated LSK−CD25+ cells uniformly express ST2, the IL-33 receptor. In addition, culture of sorted LSK−CD25+ cells showed that they indeed produce IL-5 and IL-13 when cultured with IL-33 plus IL-2 and IL-33 plus IL-7. Furthermore, i.p. injections of IL-33 or IL-25 into mice induced LSK−CD25+ cells to expand, in both size and frequency, and to upregulate ST2 and α4β7 integrin, a mucosal homing marker. Thus, we identify the enigmatic bone marrow LSK−CD25+ cells as IL-33 responsive, both in vitro and in vivo, with attributes similar to other type 2 innate cells described in peripheral tissues.
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影响因子：
5.4
作者：
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通讯作者：
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DOI：
10.1073/pnas.0812690106
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