Interleukin 17 receptor A modulates monocyte subsets and macrophage generation in vivo.
Interleukin 17 receptor A modulates monocyte subsets and macrophage generation in vivo.
复制标题
白细胞介素 17 受体 A 调节体内单核细胞亚群和巨噬细胞的生成。
DOI：
10.1371/journal.pone.0085461
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
von Vietinghoff S
中科院分区：
文献类型：
--
作者：
Ge S;Hertel B;Susnik N;Rong S;Dittrich AM;Schmitt R;Haller H;von Vietinghoff S
白细胞介素(IL)-17A通过白细胞介素17受体A （Il17ra）发出信号，通过诱导先天免疫细胞的募集参与炎症宿主反应，但也在稳态中性粒细胞调节中发挥作用。单核细胞是另一种主要的先天免疫细胞，其寿命较长，可以通过多种途径向组织巨噬细胞分化。通过小鼠Ly6C/Gr1表面标记物的表达将单核细胞分为两个亚群。我们在此研究了Il17ra在单核细胞稳态和巨噬细胞生成中的作用。在il - 17ra-/-和混合骨髓嵌合wt/Il17ra-/-小鼠中，与wt细胞相比，循环il - 17ra-/- gr1low单核细胞的浓度显著降低。肺、脾和常驻腹膜的Il17ra-/-巨噬细胞明显少于wt源。骨髓祖细胞和单核细胞数量相等，但在骨髓水平上Il17ra-/- gr1low单核细胞的比例已经降低。单核细胞耗竭后，Il17ra-/-和wt细胞的初始Gr1high和Gr1low单核细胞再生非常相似。然而，Il17ra-/- gr1low计数没有持续。用荧光珠或BrdU标记后，与wt细胞不同，未检测到Il17ra-/- gr1high单核细胞向Gr1low细胞的转变。单核细胞募集在急性腹膜炎中，已知主要是由于gr1高细胞迁移，在相同的环境中不受影响。单侧输尿管梗阻可引起较不急性的炎症性和纤维化性肾损伤。与相同环境下的wt细胞相比，Il17ra-/-巨噬细胞在肾脏中的积累减少。在所有髓系细胞缺乏Il17ra的情况下，肾纤维化明显减弱。我们的数据显示Il17ra调节Gr1low单核细胞计数，并提示Gr1high到Gr1low单核细胞转化缺陷是潜在的机制。缺乏Il17ra改变了稳态组织巨噬细胞的形成，减少了肾脏炎症和纤维化。Il17ra似乎是一种新的单核细胞表型调节剂，可能是肾纤维化的治疗靶点。
Interleukin (IL)-17A signaling via Interleukin 17 receptor A (Il17ra) contributes to the inflammatory host response by inducing recruitment of innate immune cells, but also plays a role in homeostatic neutrophilic granulocyte regulation. Monocytes, the other main innate immune cell, have a longer life span and can pursue multiple differentiation pathways towards tissue macrophages. Monocytes are divided into two subpopulations by expression of the Ly6C/Gr1 surface marker in mice. We here investigated the role of Il17ra in monocyte homeostasis and macrophage generation. In Il17ra-/- and in mixed bone marrow chimeric wt/Il17ra-/- mice, the concentrations of circulating Il17ra-/-Gr1low monocytes were significantly decreased compared to wt cells. Pulmonary, splenic and resident peritoneal Il17ra-/- macrophages were significantly fewer than of wt origin. Bone marrow progenitor and monocyte numbers were equal, but the proportion of Il17ra-/-Gr1low monocytes was already decreased at bone marrow level. After monocyte depletion, initial Gr1high and Gr1low monocyte regeneration of Il17ra-/- and wt cells was very similar. However, Il17ra-/-Gr1low counts were not sustained. After labeling with either fluorescent beads or BrdU, Il17ra-/-Gr1high monocyte transition to Gr1low cells was not detectable unlike wt cells. Monocyte recruitment in acute peritonitis, which is known to be largely due to Gr1high cell migration, was unaffected in an identical environment. Unilateral ureteral obstruction induces a less acute inflammatory and fibrotic kidney injury. Compared to wt cells in the same environment, Il17ra-/- macrophage accumulation in the kidney was decreased. In the absence of Il17ra on all myeloid cells, renal fibrosis was significantly attenuated. Our data show that Il17ra modulates Gr1low monocyte counts and suggest defective Gr1high to Gr1low monocyte transition as an underlying mechanism. Lack of Il17ra altered homeostatic tissue macrophage formation and diminished renal inflammation and fibrosis. Il17ra appears to be a novel modulator of monocyte phenotype and possible therapeutic target in renal fibrosis.
登录
查看更多内容
IL-17RE 是 IL-17C 的功能性受体，介导针对肠道病原体感染的粘膜免疫
影响因子：
30.5
作者：
Song, Xinyang;Zhu, Shu;Qian, Youcun
通讯作者：
Qian, Youcun
影响因子：
29.4
作者：
Meng F;Wang K;Aoyama T;Grivennikov SI;Paik Y;Scholten D;Cong M;Iwaisako K;Liu X;Zhang M;Österreicher CH;Stickel F;Ley K;Brenner DA;Kisseleva T
通讯作者：
Kisseleva T
影响因子：
15.9
作者：
Koltsova, Ekaterina K.;Garcia, Zacarias;Ley, Klaus
通讯作者：
Ley, Klaus
影响因子：
16.8
作者：
Ingersoll MA;Platt AM;Potteaux S;Randolph GJ
通讯作者：
Randolph GJ
DOI：
10.1038/nri3070
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--