Aging-Related Impairments to M Cells in Peyer's Patches Coincide With Disturbances to Paneth Cells.
Aging-Related Impairments to M Cells in Peyer's Patches Coincide With Disturbances to Paneth Cells.
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DOI：
10.3389/fimmu.2021.761949
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发表时间：
2021
影响因子：
7.3
通讯作者：
Mabbott NA
中科院分区：
文献类型：
--
作者：
Donaldson DS;Shih BB;Mabbott NA
衰老过程中粘膜免疫力的下降增加了老年人对通过胃肠道和呼吸道获得的感染的易感性、发病率和死亡率。我们先前表明，这种免疫衰老包括覆盖派尔集合淋巴结的卵泡相关上皮细胞（FAE）中M细胞功能成熟的减少，从而降低了从肠腔中采集抗原和病原体的能力。在这里，mRNA-seq数据集的共表达分析揭示了老年小鼠派伊尔斑中大多数FAE和M细胞相关基因的普遍下调，包括已知对M细胞分化至关重要的关键转录因子。相反，ACE 2（SARS-Cov-2病毒的细胞受体）的表达在老年FAE中增加。这增加了老年派尔集合淋巴结对SARS-Cov-2病毒感染的易感性增加的可能性。在老年小鼠的回肠中，关键的潘氏细胞相关基因的表达也减少了，这与衰老对其功能的不利影响一致。然而，这些基因在老年小鼠绒毛上皮中的表达增加表明潘氏细胞在老年肠道中的分布受到干扰。衰老对潘氏细胞的影响对肠道上皮的再生能力产生负面影响，并可能间接阻碍M细胞分化。因此，恢复潘氏细胞功能可能代表了一种新的手段，以改善M细胞分化的老化肠和增加粘膜接种疫苗的老年人的效力。
The decline in mucosal immunity during aging increases susceptibility, morbidity and mortality to infections acquired via the gastrointestinal and respiratory tracts in the elderly. We previously showed that this immunosenescence includes a reduction in the functional maturation of M cells in the follicle-associated epithelia (FAE) covering the Peyer’s patches, diminishing the ability to sample of antigens and pathogens from the gut lumen. Here, co-expression analysis of mRNA-seq data sets revealed a general down-regulation of most FAE- and M cell-related genes in Peyer’s patches from aged mice, including key transcription factors known to be essential for M cell differentiation. Conversely, expression of ACE2, the cellular receptor for SARS-Cov-2 virus, was increased in the aged FAE. This raises the possibility that the susceptibility of aged Peyer’s patches to infection with the SARS-Cov-2 virus is increased. Expression of key Paneth cell-related genes was also reduced in the ileum of aged mice, consistent with the adverse effects of aging on their function. However, the increased expression of these genes in the villous epithelium of aged mice suggested a disturbed distribution of Paneth cells in the aged intestine. Aging effects on Paneth cells negatively impact on the regenerative ability of the gut epithelium and could indirectly impede M cell differentiation. Thus, restoring Paneth cell function may represent a novel means to improve M cell differentiation in the aging intestine and increase mucosal vaccination efficacy in the elderly.
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影响因子：
2.2
作者：
Inman, CF;Rees, LEN;Bailey, M
通讯作者：
Bailey, M
DOI：
10.1084/jem.20160659
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kanaya T;Sakakibara S;Jinnohara T;Hachisuka M;Tachibana N;Hidano S;Kobayashi T;Kimura S;Iwanaga T;Nakagawa T;Katsuno T;Kato N;Akiyama T;Sato T;Williams IR;Ohno H
通讯作者：
Ohno H
影响因子：
6.7
作者：
Donaldson DS;Sehgal A;Rios D;Williams IR;Mabbott NA
通讯作者：
Mabbott NA
影响因子：
5.3
作者：
de Lau, Wim;Kujala, Pekka;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H