IL-17 Promotes Differentiation of Splenic LSK(-) Lymphoid Progenitors into B Cells following Plasmodium yoelii Infection.
IL-17 Promotes Differentiation of Splenic LSK(-) Lymphoid Progenitors into B Cells following Plasmodium yoelii Infection.
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DOI：
10.4049/jimmunol.1601972
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发表时间：
2017-09-01
期刊：
影响因子：
--
通讯作者：
Stumhofer JS
中科院分区：
文献类型：
--
作者：
Ghosh D;Brown SL;Stumhofer JS
LSK-（谱系-Sca-1+c-kit-）细胞是一种淋巴样祖细胞群，在脾脏中扩增，并优先分化为成熟的B细胞，以响应小鼠中约氏疟原虫感染。此外，LSK-衍生的B细胞随后可以通过产生寄生虫特异性抗体分泌细胞以及生发中心和记忆B细胞来促进持续的免疫应答。然而，感染后促进其在脾脏中分化为B细胞的因素尚未确定。在这里，我们表明，LSK−细胞产生细胞因子IL-17响应疟原虫感染。使用IL-17 ra −/−小鼠，发现除LSK−细胞外的细胞中的IL-17 R信号传导支持它们分化为B细胞。此外，在IL-17存在下生长的原代脾基质细胞通过表达IL-17 RA的podoplanin+ CD 31 −基质细胞群（与成纤维网状细胞相关的特征）增强了CXCL 12（一种与骨髓中B细胞发育相关的趋化因子）的产生。随后在体外阻断CXCL 12减少了LSK−细胞向B细胞的分化，支持这种趋化因子在这一过程中的直接作用。免疫荧光显示，podoplanin+基质细胞的红髓是主要生产者的CXCL 12约氏疟原虫感染后。此外，基质细胞上的podoplanin染色更加弥散，感染后IL-17 ra −/−小鼠中的CXCL 12染色显著减少。总之，这些结果确定了一个独特的途径，支持急性疟原虫感染期间脾脏淋巴发育。
LSK− (Lineage−Sca-1+c-kit−) cells are a lymphoid progenitor population that expands in the spleen and preferentially differentiates into mature B cells in response to Plasmodium yoelii infection in mice. Furthermore, LSK− derived B cells can subsequently contribute to the ongoing immune response through the generation of parasite-specific antibody secreting cells, and germinal center and memory B cells. However, the factors that promote their differentiation into B cells in the spleen after infection are not defined. Here we show that LSK− cells produce the cytokine IL-17 in response to Plasmodium infection. Using Il-17ra−/− mice IL-17R signaling in cells other than LSK− cells was found to support their differentiation into B cells. Moreover, primary splenic stromal cells grown in the presence of IL-17 enhanced the production of CXCL12, a chemokine associated with B-cell development in the bone marrow, by a population of IL-17RA–expressing podoplanin+CD31− stromal cells, a profile associated with fibroblastic reticular cells. Subsequent blockade of CXCL12 in vitro reduced differentiation of LSK− cells into B cells, supporting a direct role for this chemokine in this process. Immunofluorescence indicated that podoplanin+ stromal cells in the red pulp were the primary producers of CXCL12 after P. yoelii infection. Furthermore, podoplanin staining on stromal cells was more diffuse, and CXCL12 staining was dramatically reduced in Il-17ra−/− mice after infection. Together these results identify a distinct pathway that supports lymphoid development in the spleen during acute Plasmodium infection.
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