Immune responses require complex, spatially coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualize a limited number of immune-related macromolecules in situ, functioning as surrogates for cell types or processes of interest. However, this inevitably provides a limited snapshot of the tissue's immune landscape. Recent developments in high-throughput spatial -omics technologies, particularly spatial transcriptomics, and its application to human samples has facilitated a more comprehensive understanding of tissue immunity by mapping fine-grained immune cell states to their precise tissue location while providing contextual information about their immediate cellular and tissue environment. These data provide opportunities to investigate mechanisms underlying the spatial distribution of immune cells and its functional implications, including the identification of immune niches, although the criteria used to define this term have been inconsistent. Here, we review recent technological and analytic advances in multiparameter spatial profiling, focusing on how these methods have generated new insights in translational immunology. We propose a 3-step framework for the definition and characterization of immune niches, which is powerfully facilitated by new spatial profiling methodologies. Finally, we summarize current approaches to analyze adaptive immune repertoires and lymphocyte clonal expansion in a spatially resolved manner.

中文翻译：

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分析空间组学时代的免疫细胞组织生态位。


免疫反应需要免疫细胞与其组织环境之间复杂、空间协调的相互作用。几十年来，我们一直在对组织切片进行成像，以原位可视化有限数量的免疫相关大分子，作为目标细胞类型或过程的替代物。然而，这不可避免地提供了组织免疫景观的有限快照。高通量空间组学技术的最新发展，特别是空间转录组学，及其在人类样本中的应用，通过将细粒免疫细胞状态映射到其精确的组织位置，同时提供有关其直接细胞和组织环境的上下文信息，促进了对组织免疫的更全面理解。这些数据为研究免疫细胞空间分布的潜在机制及其功能意义提供了机会，包括免疫生态位的鉴定，尽管用于定义该术语的标准并不一致。在这里，我们回顾了多参数空间分析的最新技术和分析进展，重点关注这些方法如何在转化免疫学中产生新的见解。我们提出了一个用于定义和表征免疫生态位的 3 步框架，新的空间分析方法有力地促进了这一框架。最后，我们总结了当前以空间分辨方式分析适应性免疫库和淋巴细胞克隆扩增的方法。