Local antigen encounter promotes generation of tissue-resident memory T cells in the large intestine

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-10-01 DOI:10.1016/j.mucimm.2024.05.005
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Abstract

Upon infection, CD8+ T cells that have been primed in the draining lymph nodes migrate to the invaded tissue, where they receive cues prompting their differentiation into tissue-resident memory cells (Trm), which display niche-specific transcriptional features. Despite the importance of these cells, our understanding of their molecular landscape and the signals that dictate their development remains limited, particularly in specific anatomical niches such as the large intestine (LI). Here, we report that LI Trm-generated following oral infection exhibits a distinct transcriptional profile compared to Trm in other tissues. Notably, we observe that local cues play a crucial role in the preferential establishment of LI Trm, favoring precursors that migrate to the tissue early during infection. Our investigations identify cognate antigen recognition as a major driver of Trm differentiation at this anatomical site. Local antigen presentation not only promotes the proliferation of effector cells and memory precursors but also facilitates the acquisition of transcriptional features characteristic of gut Trm. Thus, antigen recognition in the LI favors the establishment of Trm by impacting T cell expansion and gene expression.
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局部抗原相遇可促进大肠中组织驻留记忆 T 细胞的生成。
感染后,在引流淋巴结中被激活的 CD8+ T 细胞会迁移到受侵袭的组织,在那里它们会接收到促使它们分化为组织驻留记忆细胞(Trm)的信号,这些细胞会显示出龛位特异性转录特征。尽管这些细胞非常重要,但我们对其分子图谱和决定其发育的信号的了解仍然有限,尤其是在大肠(LI)等特定解剖龛位中。在这里,我们报告了口腔感染后产生的大肠Trm与其他组织中的Trm相比表现出不同的转录特征。值得注意的是,我们观察到局部线索在 LI Trm 的优先建立中起着至关重要的作用,有利于感染期间早期迁移到该组织的前体。我们的研究发现,同源抗原识别是这一解剖部位Trm分化的主要驱动力。局部抗原呈递不仅能促进效应细胞和记忆前体的增殖,还能促进获得肠道Trm特有的转录特征。因此,LI 中的抗原识别会影响 T 细胞的扩增和基因表达,从而有利于 Trm 的建立。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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