Bellomo Alicia, Gentek Rebecca, Golub Rachel, Bajénoff Marc
CIRI, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, Lyon, France.
Centre for Inflammation Research & Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Immunol Rev. 2021 Jul;302(1):104-125. doi: 10.1111/imr.12979. Epub 2021 May 24.
Macrophages are an integral part of all organs in the body, where they contribute to immune surveillance, protection, and tissue-specific homeostatic functions. This is facilitated by so-called niches composed of macrophages and their surrounding stroma. These niches structurally anchor macrophages and provide them with survival factors and tissue-specific signals that imprint their functional identity. In turn, macrophages ensure appropriate functioning of the niches they reside in. Macrophages thus form reciprocal, mutually beneficial circuits with their cellular niches. In this review, we explore how this concept applies to the spleen, a large secondary lymphoid organ whose primary functions are to filter the blood and regulate immunity. We first outline the splenic micro-anatomy, the different populations of splenic fibroblasts and macrophages and their respective contribution to protection of and key physiological processes occurring in the spleen. We then discuss firmly established and potential cellular circuits formed by splenic macrophages and fibroblasts, with an emphasis on the molecular cues underlying their crosstalk and their relevance to splenic functionality. Lastly, we conclude by considering how these macrophage-fibroblast circuits might be impaired by aging, and how understanding these changes might help identify novel therapeutic avenues with the potential of restoring splenic functions in the elderly.
巨噬细胞是机体所有器官不可或缺的一部分，它们在其中参与免疫监视、保护以及组织特异性稳态功能。这得益于由巨噬细胞及其周围基质组成的所谓生态位。这些生态位在结构上固定巨噬细胞，并为它们提供生存因子和组织特异性信号，从而赋予其功能特性。反过来，巨噬细胞确保它们所驻留的生态位正常运作。因此，巨噬细胞与其细胞生态位形成了相互的、互利的循环。在本综述中，我们探讨这一概念如何适用于脾脏，脾脏是一个大型二级淋巴器官，其主要功能是过滤血液和调节免疫。我们首先概述脾脏的微观解剖结构、脾脏成纤维细胞和巨噬细胞的不同群体，以及它们对脾脏保护和发生在脾脏中的关键生理过程的各自贡献。然后，我们讨论由脾脏巨噬细胞和成纤维细胞形成的既定和潜在的细胞循环，重点关注其相互作用的分子线索及其与脾脏功能的相关性。最后，我们通过考虑衰老如何损害这些巨噬细胞 - 成纤维细胞循环，以及理解这些变化如何有助于识别具有恢复老年人脾脏功能潜力的新治疗途径来得出结论。
