Unveiling an Important New Cell Type in the Lung: Microfold Cells.
Unveiling an Important New Cell Type in the Lung: Microfold Cells.
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揭示肺中一种重要的新细胞类型：微折叠细胞。
DOI：
10.1165/rcmb.2024-0002ed
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发表时间：
2024
影响因子：
6.4
通讯作者：
Han,SeungHye
中科院分区：
文献类型：
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作者：
Han,SeungHye
哺乳动物的肺部直接暴露于环境病原体和毒素，并进化出了复杂的防御机制，包括粘膜纤毛自动扶梯和分泌抗菌肽以捕获和清除气道中的异物颗粒和微生物。新技术的进步现在使我们能够识别呼吸道中以前未曾表征过的稀有细胞类型。在该杂志最近的两期中，两个独立小组（1、2）的研究报告了肺部的一种罕见的气道上皮细胞类型。它与其他上皮细胞不同，具有与肠微褶皱 (M) 细胞相似的基因表达模式，肠微褶皱 (M) 细胞能够进行转胞吞作用以进行粘膜免疫监视（图 1）。 M 细胞是在覆盖肠道相关淋巴组织的上皮中发现的特殊肠上皮细胞，例如小肠中的派耶尔氏斑 (3, 4)。 M 细胞吸收细菌、病毒和颗粒等管腔抗原，并将它们输送到下面的淋巴滤泡，在那里它们可以与抗原呈递细胞和 B 淋巴细胞相互作用，提供独特的粘膜免疫监视系统。与其他肠上皮细胞相比，M细胞具有独特的形态，因为它们的顶端表面有短的或缺乏微绒毛，并且在其基底外侧表面有袋状内陷（即M细胞袋），其中含有树突状细胞和淋巴细胞。 M 细胞构成小鼠和人类肠滤泡相关上皮的 5-10% (3)，并以多种标记基因和蛋白质为特征。糖蛋白 2 (GP2) 在成熟 M 细胞上特异性表达，并充当微生物摄取受体。 Marcksl1（富含肉豆蔻酰化丙氨酸的蛋白激酶 C 底物 like-1）、Tnfaip2、Anxa5、Ccl9、Spi-B 和 Sox8 也是 M 细胞分化早期表达的标记基因。 M 细胞源自肠上皮干细胞，由 TNF 超家族细胞因子 RANKL（NF-κB 配体受体激活剂）诱导。尽管 M 细胞在肠道中得到了最好的描述，但据报道，M 细胞存在于覆盖鼻咽相关淋巴组织 (NALT) 的上呼吸道 (5, 6)。与肠道 M 细胞类似，NALT M 细胞可以吸收管腔微生物和颗粒 (5-7) 并表达成熟的肠道 M 细胞标记物 GP2 以及其他肠道 M 细胞标记物，如 Tnfaip2、CCL9 和 Spi-B (7)。 NALT M 细胞也由 RANKL-RANK 信号传导诱导 (7)。与肠道或鼻咽不同，肺部的微生物负荷非常低，长期以来被认为是无菌的。然而，腹膜内施用 RANKL 后，小鼠气管中的少量 M 细胞确实会扩增 (8)。气管 M 细胞还能够进行转胞吞作用，并且与小鼠中病理诱导的支气管相关淋巴组织 (BALT) 存在空间相关性 (8)。这些细胞的细胞起源以及M细胞是否存在于肺部远端气道中仍然未知。在最近的研究中，两个小组都使用单细胞或单核RNA测序，发现了一种以前在肺部中未报道过的罕见细胞类型。 Surve 及其同事 (1) 重新分析了已发表的单细胞 RNA 测序数据 (9)，并揭示了稳态小鼠气管中存在稀有 M 细胞。气管 M 细胞表达肠道 M 细胞特有的基因，例如
Mammalian lungs are directly exposed to environmental pathogens and toxins and have evolved complex defense mechanisms, including the mucociliary escalator and secretion of antimicrobial peptides to trap and remove foreign particles and microbes from the airways. Advances in new technologies are now allowing us to identify rare cell types in the respiratory tract that have not been characterized before. In two recent issues of the Journal, studies from two independent groups (1, 2) report on a rare airway epithelial cell type in the lung. It is distinct from other epithelial cells and has gene expression patterns similar to intestinal microfold (M) cells, epithelial cells capable of transcytosis for mucosal immune surveillance (Figure 1). M cells are specialized intestinal epithelial cells found in the epithelium covering gut-associated lymphoid tissue, such as the Peyeres patches in the small intestine (3, 4). M cells take up luminal antigens such as bacteria, viruses, and particles and deliver them to the underlying lymphoid follicles, where they can interact with antigen-presenting cells and B lymphocytes to provide a unique mucosal immune surveillance system. M cells have a distinctive morphology compared with other intestinal epithelial cells in that they have short or absent microvilli on their apical surface and a pocket-like invagination (ie, M cell pocket) on their basolateral surface that harbors dendritic cells and lymphocytes. M cells constitute 5-10% of the intestinal follicle-associated epithelium in mice and humans (3) and are characterized by several marker genes and proteins. Glycoprotein 2 (GP2) is specifically expressed on mature M cells and functions as a microbial uptake receptor. Marcksl1 (myristoylated alanine rich protein kinase C substrate like-1), Tnfaip2, Anxa5, Ccl9, Spi-B, and Sox8 are also marker genes that are expressed early during M cell differentiation. M cells are derived from intestinal epithelial stem cells, induced by the TNF superfamily cytokine RANKL (receptor activator of NF-κB ligand). Although M cells are best described in the gut, M cells have been reported in the upper respiratory tract overlying the nasopharynxassociated lymphoid tissue (NALT)(5, 6). Similar to the intestinal M cells, NALT M cells can take up luminal microbes and particles (5-7) and express the mature intestinal M cell marker GP2 as well as other intestinal M cell markers such as Tnfaip2, CCL9, and Spi-B (7). NALT M cells are also induced by RANKL-RANK signaling (7). Unlike the gut or the nasopharynx, the lung has a very low microbial load and was long considered sterile. Nevertheless, a small number of M cells in the mouse trachea do expand upon intraperitoneal administration of RANKL (8). Tracheal M cells are also capable of transcytosis and are spatially associated with pathologically induced bronchus-associated lymphoid tissue (BALT) in mice (8). The cellular origin of these cells and whether M cells exist in the distal airways of the lung remained unknown.In the recent studies, both groups used single-cell or singlenucleus RNA sequencing and discovered a rare cell type not previously reported in the lung. Surve and colleagues (1) reanalyzed published single-cell RNA sequencing data (9) and revealed the existence of rare M cells in the homeostatic mouse trachea. Tracheal M cells express genes that are characteristic of intestinal M cells, such