T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo
T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo
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DOI：
10.1101/2020.08.21.261073
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发表时间：
2020-08
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通讯作者：
Jan-Hendrik Schroeder;N. Garrido-Mesa;T. Zabinski;A. Gallagher;L. Campbell;L. Roberts;É. Stolarczyk;G. Beattie;J. Lo;A. Iseppon;C. M. Heliodoro;R. Reis;RG Jenner;P. Lavender;J. Howard;R. Grencis;H. Helmby;J. Neves;G. Lord
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作者：
Jan-Hendrik Schroeder;N. Garrido-Mesa;T. Zabinski;A. Gallagher;L. Campbell;L. Roberts;É. Stolarczyk;G. Beattie;J. Lo;A. Iseppon;C. M. Heliodoro;R. Reis;RG Jenner;P. Lavender;J. Howard;R. Grencis;H. Helmby;J. Neves;G. Lord
先天性淋巴样细胞（ILC）在调节粘膜表面的免疫反应中起着关键作用。存在类似于由特定转录因子的表达定义的T细胞谱系的各种亚群。因此，T-bet在ILC1和Th1细胞中表达。为了进一步了解T-bet在ILC中的功能作用，我们产生了一种命运定位小鼠模型，该模型永久标记了表达或曾经表达T-bet的细胞及其后代。在这里，我们已经鉴定并表征了一种具有ILC1和ILC2特征的新型ILC，其对于T-bet表达是"命运映射"的，并且在建立成熟微生物组之前在新生儿生命早期出现。这些ILC1-ILC2细胞严重依赖于T-bet，并且能够在稳态下表达1型和2型细胞因子，但在炎症的情况下不表达。这些发现完善了我们对ILC谱系调节和稳定性的理解，并对理解粘膜表面的ILC生物学具有重要意义。先天性淋巴样细胞（ILC）在调节粘膜表面的免疫应答中起着关键作用。根据定义转录因子和其他标记物的子集的表达，已经描述了三种不同的ILC组。在这项研究中，我们描述了一个新的ILC子集的特点，组1和组2 ILC在体内。
Innate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are “fate-mapped” for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces. SUMMARY Innate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.