Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function.
Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function.
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DOI：
10.1038/s41467-022-29734-2
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发表时间：
2022-04-19
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
先天性淋巴样细胞（ILC）控制肠道中的免疫细胞稳态，并保护宿主免受微生物病原体的侵害。已经确定了决定ILC发育和分化的各种细胞内在途径。然而，调节ILC在肠固有层中的维持和功能的细胞组分却鲜为人知。使用固有层成纤维细胞的单细胞转录组学分析，我们确定成纤维网状细胞（FRC）的基础cryptopatches（CP）和孤立的淋巴滤泡（ILF）。在表达Ccl 19的FRC中基因切除光氧素-β受体表达可阻断CP成熟为成熟ILF。相互作用组分析显示了FRC-ILC串扰的主要利基因素和过程。体内验证证实，FRC激活（包括IL-7生成）的持续光敏素驱动的前馈环路对于维持功能性ILC群体至关重要。总之，我们的研究表明，关键的成纤维细胞壁龛内的肠固有层，控制ILC的稳态和功能，从而确保保护肠道免疫。成纤维网状细胞（FRC）支持免疫细胞在次级淋巴组织中的定位，但对固有层的了解较少。在这里，作者使用scRNA-seq和肠道感染来抑制肠道固有层中的FRC，并显示在稳态和感染过程中培养先天淋巴细胞的专门小生境。
Innate lymphoid cells (ILCs) govern immune cell homeostasis in the intestine and protect the host against microbial pathogens. Various cell-intrinsic pathways have been identified that determine ILC development and differentiation. However, the cellular components that regulate ILC sustenance and function in the intestinal lamina propria are less known. Using single-cell transcriptomic analysis of lamina propria fibroblasts, we identify fibroblastic reticular cells (FRCs) that underpin cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Genetic ablation of lymphotoxin-β receptor expression in Ccl19-expressing FRCs blocks the maturation of CPs into mature ILFs. Interactome analysis shows the major niche factors and processes underlying FRC-ILC crosstalk. In vivo validation confirms that a sustained lymphotoxin-driven feedforward loop of FRC activation including IL-7 generation is critical for the maintenance of functional ILC populations. In sum, our study indicates critical fibroblastic niches within the intestinal lamina propria that control ILC homeostasis and functionality and thereby secure protective gut immunity. Fibroblastic reticular cells (FRCs) support localisation of immune cells in secondary lymphoid tissues but less is known about the lamina propria. Here the authors use scRNA-seq and intestinal infection to characterise FRCs in the intestinal lamina propria and show specialised niches that foster innate lymphoid cells during homeostasis and infection.
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影响因子：
64.5
作者：
Kinchen J;Chen HH;Parikh K;Antanaviciute A;Jagielowicz M;Fawkner-Corbett D;Ashley N;Cubitt L;Mellado-Gomez E;Attar M;Sharma E;Wills Q;Bowden R;Richter FC;Ahern D;Puri KD;Henault J;Gervais F;Koohy H;Simmons A
通讯作者：
Simmons A
DOI：
10.1007/978-1-4939-6786-5_17
发表时间：
2017-01-01
期刊：
INFLAMMATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gronke, Konrad;Kofoed-Nielsen, Michael;Diefenbach, Andreas
通讯作者：
Diefenbach, Andreas
影响因子：
64.8
作者：
Bouskra, Djahida;Brezillon, Christophe;Eberl, Gerard
通讯作者：
Eberl, Gerard
影响因子：
30.5
作者：
Bernink, Jochem H.;Peters, Charlotte P.;Spits, Hergen
通讯作者：
Spits, Hergen
影响因子：
30.5
作者：
Lee, Jacob S.;Cella, Marina;McDonald, Keely G.;Garlanda, Cecilia;Kennedy, Gregory D.;Nukaya, Manabu;Mantovani, Alberto;Kopan, Raphael;Bradfield, Christopher A.;Newberry, Rodney D.;Colonna, Marco
通讯作者：
Colonna, Marco