IL7Rα, but not Flk2, is required for hematopoietic stem cell reconstitution of tissue-resident lymphoid cells.
IL7Rα, but not Flk2, is required for hematopoietic stem cell reconstitution of tissue-resident lymphoid cells.
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DOI：
10.1242/dev.200139
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发表时间：
2022-04-15
期刊：
影响因子：
--
通讯作者：
Forsberg EC
中科院分区：
文献类型：
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作者：
Worthington AK;Cool T;Poscablo DM;Hussaini A;Beaudin AE;Forsberg EC
组织驻留淋巴样细胞（TlCs）跨越先天免疫功能到适应性免疫功能的范围。与从造血干细胞（HSC）连续产生的传统循环淋巴细胞不同，许多TLC是胎儿来源的，并且很少从成人HSC产生。在这里，我们试图进一步了解小鼠TLC的发展和Flk 2和IL 7 R α的作用，这两种细胞因子受体在传统的淋巴细胞生成中具有已知的功能。Flk 2-和IL 7 r-Cre谱系示踪发现，腹腔B1 a细胞、脾边缘带B（MZ B）细胞、肺ILC 2和调节性T细胞（Tcl 2）均被高度标记。尽管高标记，Flk 2的损失最小限度地影响这些细胞的产生。相比之下，IL 7 R α的缺失或Flk 2和IL 7 R α的联合缺失显著减少了原位和移植后B1 a细胞、MZB、ILC 2和TbR的数量，表明IL 7 R α的内在和重要作用。令人惊讶的是，野生型HSC的相互移植表明，与原位TLC数量相比，IL 7 R α−/−环境选择性地损害了TLC的重建。综上所述，我们的数据定义了Flk 2和IL 7 R α阳性TLC分化路径，并揭示了Flk 2和IL 7 R α在TLC建立中的功能作用。总结：组织驻留淋巴样细胞通过IL 7 R α阳性祖细胞发育，并通过移植的成体造血干细胞重新增殖;然而，这种TLC淋巴细胞生成在IL 7 R α−/−受体小鼠中不能完全挽救。
Tissue-resident lymphoid cells (TLCs) span the spectrum of innate-to-adaptive immune function. Unlike traditional, circulating lymphocytes that are continuously generated from hematopoietic stem cells (HSCs), many TLCs are of fetal origin and poorly generated from adult HSCs. Here, we sought to further understand murine TLC development and the roles of Flk2 and IL7Rα, two cytokine receptors with known function in traditional lymphopoiesis. Using Flk2- and Il7r-Cre lineage tracing, we found that peritoneal B1a cells, splenic marginal zone B (MZB) cells, lung ILC2s and regulatory T cells (Tregs) were highly labeled. Despite high labeling, loss of Flk2 minimally affected the generation of these cells. In contrast, loss of IL7Rα, or combined deletion of Flk2 and IL7Rα, dramatically reduced the number of B1a cells, MZBs, ILC2s and Tregs, both in situ and upon transplantation, indicating an intrinsic and essential role for IL7Rα. Surprisingly, reciprocal transplants of wild-type HSCs showed that an IL7Rα−/− environment selectively impaired reconstitution of TLCs when compared with TLC numbers in situ. Taken together, our data defined Flk2- and IL7Rα-positive TLC differentiation paths, and revealed functional roles of Flk2 and IL7Rα in TLC establishment. Summary: Tissue-resident lymphoid cells develop via IL7Rα-positive progenitors and are repopulated by transplanted adult hematopoietic stem cells; however, such TLC lymphopoiesis cannot be fully rescued in IL7Rα−/− recipient mice.