SIRPα/CD172a and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen.

SIRPα/CD172a and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen.
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DOI:
10.4049/jimmunol.1103086
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发表时间:
2012-05-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Fingeroth JD
Fingeroth JD
中科院分区:
其他
文献类型:
--
作者:
Ogembo JG;Milner DA Jr;Mansfield KG;Rodig SJ;Murphy GF;Kutok JL;Pinkus GS;Fingeroth JD

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无脾个体不仅破坏感染因子的能力受到损害,而且因自身免疫性疾病、某些肿瘤和缺血性心脏病而死亡的风险增加。死亡率增加是由于脾脏中缺乏有效吞噬和破坏适当目标的吞噬细胞,尽管在其他地方也发现了相关细胞。为了确定是否有一个独特的群体调节红细胞病原体清除和改变自身的过滤,我们回顾了解剖学文献,并通过免疫组织化学和免疫荧光原位分析了一种特征很少的细胞的表达模式,该细胞在人类和密切相关的灵长类动物的脾红髓中占主导地位,即静脉窦内壁或滨细胞(LC)。 formin FHOD1 的高表达勾画出了 LC 群体。尽管 LC 的分布与内皮细胞类似,但它们表达多种巨噬细胞定向蛋白、红细胞抗原 DARC 和 T 细胞共受体 CD8α/α,但它们缺乏谱系相关标记 CD34 和 CD45。引人注目的是,SIRPα (CD172a) 在人脾中的表达集中在 LC 上,这与最近证明的在红细胞周转和消除与释放感染或改变的自身中的关键作用一致。我们的结果表明,人类 LC(SIRPα+、FHOD1+、CD8α/α+、CD34−、CD45−)包含高度可塑性的屏障细胞群,该细胞群在灵长类进化后期出现,与 CD8 表达相协调。 LC 是人科动物所特有的,可能是细胞在通过人脾脏后重新循环的最终决定因素。
Asplenic individuals are compromised not only in their ability to destroy infectious agents, but are at increased risk of death from autoimmune disease, certain tumors, and ischemic heart disease. Enhanced mortality is attributed to lack of phagocytes sequestered in spleen that efficiently engulf and destroy appropriate targets, though related cells are found elsewhere. To determine whether a unique population regulates RBC-pathogen clearance and filtration of altered self, we reviewed the anatomic literature and analyzed in situ by immunohistochemistry and immunofluorescence the expression patterns of a little-characterized cell that dominates the splenic red pulp of man and closely related primates-the venous sinus lining or littoral cell (LC). High expression of the formin FHOD1 outlines the LC population. Though LCs are endothelial-like in distribution they express several macrophage directed proteins, the RBC antigen DARC and T-cell co-receptor CD8α/α yet they lack lineage-associated markers CD34 and CD45. Strikingly, SIRPα (CD172a) expression in human spleen concentrates on LCs, consistent with recent demonstration of a key role in RBC turnover and elimination versus release of infected or altered self. Our results indicate human LCs (SIRPα+, FHOD1+, CD8α/α+, CD34−, CD45−) comprise a highly plastic barrier cell population that emerged late in primate evolution coordinate with CD8 expression. Unique to Hominidae, LCs may be the ultimate determinant of which cells re-circulate after passage through human spleen.
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