PDF(Pubmed)
Abstract：
BACKGROUND: The establishment of microbial communities in neonatal mammals plays a pivotal role in shaping their immune responses to infections and other immune-related conditions. This process is influenced by a combination of endogenous and exogenous factors. Previously, we reported that depletion of CD71 + erythroid cells (CECs) results in an inflammatory response to microbial communities in newborn mice.
RESULTS: Here, we systemically tested this hypothesis and observed that the small intestinal lamina propria of neonatal mice had the highest frequency of CECs during the early days of life. This high abundance of CECs was attributed to erythropoiesis niches within the small intestinal tissues. Notably, the removal of CECs from the intestinal tissues by the anti-CD71 antibody disrupted immune homeostasis. This disruption was evident by alteration in the expression of antimicrobial peptides (AMPs), toll-like receptors (TLRs), inflammatory cytokines/chemokines, and resulting in microbial dysbiosis. Intriguingly, these alterations in microbial communities persisted when tested 5 weeks post-treatment, with a more notable effect observed in female mice. This illustrates a sex-dependent association between CECs and neonatal microbiome modulation. Moreover, we extended our studies on pregnant mice, observing that modulating CECs substantially alters the frequency and diversity of their microbial communities. Finally, we found a significantly lower proportion of CECs in the cord blood of pre-term human newborns, suggesting a potential role in dysregulated immune responses to microbial communities in the gut.
CONCLUSIONS: Our findings provide novel insights into pivotal role of CECs in immune homeostasis and swift adaptation of microbial communities in newborns. Despite the complexity of the cellular biology of the gut, our findings shed light on the previously unappreciated role of CECs in the dialogue between the microbiota and immune system. These findings have significant implications for human health. Video Abstract.
RESULTS: Here, we systemically tested this hypothesis and observed that the small intestinal lamina propria of neonatal mice had the highest frequency of CECs during the early days of life. This high abundance of CECs was attributed to erythropoiesis niches within the small intestinal tissues. Notably, the removal of CECs from the intestinal tissues by the anti-CD71 antibody disrupted immune homeostasis. This disruption was evident by alteration in the expression of antimicrobial peptides (AMPs), toll-like receptors (TLRs), inflammatory cytokines/chemokines, and resulting in microbial dysbiosis. Intriguingly, these alterations in microbial communities persisted when tested 5 weeks post-treatment, with a more notable effect observed in female mice. This illustrates a sex-dependent association between CECs and neonatal microbiome modulation. Moreover, we extended our studies on pregnant mice, observing that modulating CECs substantially alters the frequency and diversity of their microbial communities. Finally, we found a significantly lower proportion of CECs in the cord blood of pre-term human newborns, suggesting a potential role in dysregulated immune responses to microbial communities in the gut.
CONCLUSIONS: Our findings provide novel insights into pivotal role of CECs in immune homeostasis and swift adaptation of microbial communities in newborns. Despite the complexity of the cellular biology of the gut, our findings shed light on the previously unappreciated role of CECs in the dialogue between the microbiota and immune system. These findings have significant implications for human health. Video Abstract.
摘要：
背景：新生哺乳动物中微生物群落的建立在塑造其对感染和其他免疫相关疾病的免疫应答中起着关键作用。这一过程受到内源性和外源性因素的共同影响。以前,我们报道,CD71+红系细胞(CECs)的耗竭导致新生小鼠对微生物群落的炎症反应.
结果：这里，我们系统地检验了这一假设,并观察到新生小鼠的小肠固有层在生命早期出现CECs的频率最高.这种高丰度的CEC归因于小肠组织内的红细胞生成生态位。值得注意的是,通过抗CD71抗体从肠组织中去除CEC破坏了免疫稳态。通过改变抗菌肽（AMP）的表达，这种破坏是显而易见的。toll样受体（TLRs），炎性细胞因子/趋化因子，导致微生物菌群失调。有趣的是，在治疗后5周进行测试时，微生物群落的这些变化仍然存在，在雌性小鼠中观察到更显著的效果。这说明了CEC与新生儿微生物组调节之间的性别依赖性关联。此外，我们扩展了对怀孕老鼠的研究，观察到调节CEC会显著改变其微生物群落的频率和多样性。最后,我们发现早产新生儿脐带血中CECs的比例明显较低，提示在肠道微生物群落失调的免疫反应中的潜在作用。
结论：我们的发现为CECs在新生儿免疫稳态和微生物群落快速适应中的关键作用提供了新的见解。尽管肠道细胞生物学的复杂性，我们的研究结果揭示了CECs在微生物群和免疫系统之间的对话中以前未被重视的作用.这些发现对人类健康具有重要意义。视频摘要。
结果：这里，我们系统地检验了这一假设,并观察到新生小鼠的小肠固有层在生命早期出现CECs的频率最高.这种高丰度的CEC归因于小肠组织内的红细胞生成生态位。值得注意的是,通过抗CD71抗体从肠组织中去除CEC破坏了免疫稳态。通过改变抗菌肽（AMP）的表达，这种破坏是显而易见的。toll样受体（TLRs），炎性细胞因子/趋化因子，导致微生物菌群失调。有趣的是，在治疗后5周进行测试时，微生物群落的这些变化仍然存在，在雌性小鼠中观察到更显著的效果。这说明了CEC与新生儿微生物组调节之间的性别依赖性关联。此外，我们扩展了对怀孕老鼠的研究，观察到调节CEC会显著改变其微生物群落的频率和多样性。最后,我们发现早产新生儿脐带血中CECs的比例明显较低，提示在肠道微生物群落失调的免疫反应中的潜在作用。
结论：我们的发现为CECs在新生儿免疫稳态和微生物群落快速适应中的关键作用提供了新的见解。尽管肠道细胞生物学的复杂性，我们的研究结果揭示了CECs在微生物群和免疫系统之间的对话中以前未被重视的作用.这些发现对人类健康具有重要意义。视频摘要。
