PDF(Pubmed)
Abstract：
UNASSIGNED: The caecum bridges the small and large intestine and plays a front-line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically.
UNASSIGNED: To address this issue, we applied single-cell transcriptomic-V(D)J sequencing to FACS-isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5-year-old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues.
UNASSIGNED: We found caecal NK cells and ILC3s to co-exist with a spectrum of effector T cells partially derived from SOX4 + recent thymic emigrants. Tolerogenic Vγ8Vδ1-T cells, plastic CD4+ T helper cells and GZMK + EOMES + and TMIGD2 + tissue-resident memory CD8+ T cells were present and differed metabolically. An IL13 + GATA3 + Th2 subset expressing eicosanoid pathway enzymes was accompanied by IL1RL1 + GATA3 + regulatory T cells and a minor proportion of IgE+ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen-presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into IGF1 + PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies.
UNASSIGNED: The data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.
UNASSIGNED: To address this issue, we applied single-cell transcriptomic-V(D)J sequencing to FACS-isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5-year-old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues.
UNASSIGNED: We found caecal NK cells and ILC3s to co-exist with a spectrum of effector T cells partially derived from SOX4 + recent thymic emigrants. Tolerogenic Vγ8Vδ1-T cells, plastic CD4+ T helper cells and GZMK + EOMES + and TMIGD2 + tissue-resident memory CD8+ T cells were present and differed metabolically. An IL13 + GATA3 + Th2 subset expressing eicosanoid pathway enzymes was accompanied by IL1RL1 + GATA3 + regulatory T cells and a minor proportion of IgE+ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen-presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into IGF1 + PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies.
UNASSIGNED: The data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.
摘要：
■盲肠桥接小肠和大肠，在区分胃肠道抗原中起着前线作用。尽管在急性和慢性疾病中失调，该组织在免疫学上经常被忽视。
■要解决此问题，我们将单细胞转录组学-V(D)J测序应用于FACS离体分离的健康(5岁)雌性恒河猴的CD45+盲肠补片/固有层白细胞,并将这些数据与来自造血组织的VDJ深度测序读数相关联.
■我们发现盲肠NK细胞和ILC3与一系列部分源自SOX4+最近胸腺移民的效应T细胞共存。致耐受性Vγ8Vδ1-T细胞，可塑性CD4+T辅助细胞和GZMK+EOMES+和TMIGD2+组织驻留的记忆CD8+T细胞存在并且代谢不同。表达类花生酸途径酶的IL13GATA3Th2亚群伴有IL1RL1GATA3调节性T细胞和少量IgE浆细胞（PC），说明严格控制缺乏ILC2s的2型免疫。就B淋巴细胞谱系而言，盲肠贴片抗原呈递记忆B细胞与生发中心细胞一起发生体细胞超突变并分化为IGF1PC。原型基因表达特征在PC簇中减少，尤其是,扩增的IgA克隆型可以在来自其他区室的VDJ深度测序读数中追踪，包括骨髓,支持这些细胞提供稳定的全身性抗体流。
■这些数据促进了我们对盲肠免疫功能的理解，揭示与疾病有关的屏障维持和分子网络的过程。
■要解决此问题，我们将单细胞转录组学-V(D)J测序应用于FACS离体分离的健康(5岁)雌性恒河猴的CD45+盲肠补片/固有层白细胞,并将这些数据与来自造血组织的VDJ深度测序读数相关联.
■我们发现盲肠NK细胞和ILC3与一系列部分源自SOX4+最近胸腺移民的效应T细胞共存。致耐受性Vγ8Vδ1-T细胞，可塑性CD4+T辅助细胞和GZMK+EOMES+和TMIGD2+组织驻留的记忆CD8+T细胞存在并且代谢不同。表达类花生酸途径酶的IL13GATA3Th2亚群伴有IL1RL1GATA3调节性T细胞和少量IgE浆细胞（PC），说明严格控制缺乏ILC2s的2型免疫。就B淋巴细胞谱系而言，盲肠贴片抗原呈递记忆B细胞与生发中心细胞一起发生体细胞超突变并分化为IGF1PC。原型基因表达特征在PC簇中减少，尤其是,扩增的IgA克隆型可以在来自其他区室的VDJ深度测序读数中追踪，包括骨髓,支持这些细胞提供稳定的全身性抗体流。
■这些数据促进了我们对盲肠免疫功能的理解，揭示与疾病有关的屏障维持和分子网络的过程。
