Aging has multifaceted effects on the immune system, but how aging affects tissue-specific immunity is not well-defined. Bladder diseases characterized by chronic inflammation are highly prevalent in older women, but mechanisms by which aging promotes these pathologies remain unknown. Tissue transcriptomics of unperturbed, young and aged bladders identified a highly altered immune landscape as a fundamental feature of the aging female bladder. Detailed mapping of immune cells using single cell RNA-sequencing revealed novel subsets of macrophages and dendritic cells and unique changes to the immune repertoire in the aged bladder. B and T cells are highly enriched in aged bladders and spontaneously form organized bladder tertiary lymphoid tissues (bTLTs). Naïve, activated, and germinal center B cells and IgA+ plasma cells are found within bTLT and associated with increased urinary IgA concentrations. bTLTs form with increasing age and their formation is dependent on TNFα. Microbiota are not required to form bTLT, as aged germfree mice also harbor them. Thus, bTLTs require age-dependent TNFα but are independent of the microbiota. Our results indicate that chronic, age-associated inflammation underlies a fundamental alteration to the bladder and establishes a resource for further investigation of the bladder immune system in homeostasis, aging, and disease.

中文翻译：

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小鼠膀胱的单细胞和组织转录组学分析揭示了年龄和 TNFα 依赖性但与微生物群无关的三级淋巴组织形成。

衰老对免疫系统有多方面的影响，但衰老如何影响组织特异性免疫尚不清楚。以慢性炎症为特征的膀胱疾病在老年女性中非常普遍，但衰老促进这些疾病的机制仍然未知。未受干扰的、年轻的和年老的膀胱的组织转录组学将高度改变的免疫环境确定为衰老女性膀胱的基本特征。使用单细胞 RNA 测序对免疫细胞进行详细定位，揭示了巨噬细胞和树突状细胞的新亚群以及老年膀胱免疫组库的独特变化。B 和 T 细胞在老化的膀胱中高度富集，并自发形成有组织的膀胱三级淋巴组织 (bTLT)。天真，活跃，在 bTLT 中发现了生发中心 B 细胞和 IgA+ 浆细胞，并且与尿 IgA 浓度增加有关。bTLTs 随着年龄的增长而形成，它们的形成依赖于 TNFα。微生物群并不是形成 bTLT 所必需的，因为年老的无菌小鼠也含有它们。因此，bTLT 需要依赖于年龄的 TNFα，但独立于微生物群。我们的结果表明，与年龄相关的慢性炎症是膀胱根本改变的基础，并为进一步研究膀胱免疫系统在稳态、衰老和疾病中的作用奠定了基础。bTLT 需要年龄依赖性 TNFα，但独立于微生物群。我们的结果表明，与年龄相关的慢性炎症是膀胱根本改变的基础，并为进一步研究膀胱免疫系统在稳态、衰老和疾病中的作用奠定了基础。bTLT 需要年龄依赖性 TNFα，但独立于微生物群。我们的结果表明，与年龄相关的慢性炎症是膀胱根本改变的基础，并为进一步研究膀胱免疫系统在稳态、衰老和疾病中的作用奠定了基础。