Microbiome diversity declines while distinct expansions of Th17, iNKT, and dendritic cell subpopulations emerge after anastomosis surgery.
Microbiome diversity declines while distinct expansions of Th17, iNKT, and dendritic cell subpopulations emerge after anastomosis surgery.
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在吻合手术后，微生物组多样性下降，同时出现了Th17、不变自然杀伤T细胞（iNKT）和树突状细胞亚群的明显扩增。
DOI：
10.1186/s13099-021-00447-z
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发表时间：
2021-08-10
期刊：
影响因子：
4.2
通讯作者：
Basson MD
中科院分区：
文献类型：
--
作者：
Vomhof-DeKrey EE;Stover A;Basson MD
即使在技术上正确的吻合术中，吻合失败也会导致发病率和死亡率。必须通过跨吻合口的粘膜重新对合来防止初始泄漏。愈合是肠上皮细胞（IEC），免疫细胞和肠道细菌之间的协同努力。IEC TLR 4激活和信号传导是粘膜愈合所需的，导致炎症因子释放，招募免疫细胞以限制细菌入侵。TLR 4缺失导致上皮细胞增殖丧失、炎症反应减弱和细菌移位导致粘膜损伤。我们假设吻合后，由于TLR 4表达的减少，微生物群将发生不平衡，并将导致免疫环境的变化。我们从小鼠、Roux-en-Y和端到端结肠炎中分离粪便内容物和小肠白细胞，以鉴定微生物组变化以及术后3天调节性和促炎性免疫细胞的后续改变。TLR 4 + IEC在吻合后受损。微生物组多样性减少，厚壁菌门、拟杆菌门和Saccharomyces细菌减少，变形菌门增加。吻合后明显的TCRβhi CD 4 + T细胞亚群是对照小鼠的10-20倍。84%为Th 17 IL-17 A/F+ IL-22+和/或TNFα+。iNKT细胞增加，TCRβhi。75%为iNKT IL-10+，13%为iNKTh 17 IL-22+。此外，Treg IL-10+和IL-22+细胞增加。在吻合区鉴定了一种新的树突状细胞亚群，其为CD 11bhi CD 103 mid，93%为IL-10+。该吻合研究表明IEC TLR 4表达和微生物组多样性降低，然后与调节性和促炎性免疫细胞和细胞因子的扩增增加相一致。定义吻合口粘膜环境可以帮助告知创新疗法，以针对过度的促炎侵袭和微生物组失衡。在线版本包含补充材料，可通过10.1186/s13099-021-00447-z获得。
Anastomotic failure causes morbidity and mortality even in technically correct anastomoses. Initial leaks must be prevented by mucosal reapproximation across the anastomosis. Healing is a concerted effort between intestinal epithelial cells (IECs), immune cells, and commensal bacteria. IEC TLR4 activation and signaling is required for mucosal healing, leading to inflammatory factor release that recruits immune cells to limit bacteria invasion. TLR4 absence leads to mucosal damage from loss in epithelial proliferation, attenuated inflammatory response, and bacteria translocation. We hypothesize after anastomosis, an imbalance in microbiota will occur due to a decrease in TLR4 expression and will lead to changes in the immune milieu. We isolated fecal content and small intestinal leukocytes from murine, Roux-en-Y and end-to-end anastomoses, to identify microbiome changes and subsequent alterations in the regulatory and pro-inflammatory immune cells 3 days post-operative. TLR4+ IECs were impaired after anastomosis. Microbiome diversity was reduced, with Firmicutes, Bacteroidetes, and Saccharibacteria decreased and Proteobacteria increased. A distinct TCRβhi CD4+ T cells subset after anastomosis was 10–20-fold greater than in control mice. 84% were Th17 IL-17A/F+ IL-22+ and/or TNFα+. iNKT cells were increased and TCRβhi. 75% were iNKT IL-10+ and 13% iNKTh17 IL-22+. Additionally, Treg IL-10+ and IL-22+ cells were increased. A novel dendritic cell subset was identified in anastomotic regions that was CD11bhi CD103mid and was 93% IL-10+. This anastomotic study demonstrated a decrease in IEC TLR4 expression and microbiome diversity which then coincided with increased expansion of regulatory and pro-inflammatory immune cells and cytokines. Defining the anastomotic mucosal environment could help inform innovative therapeutics to target excessive pro-inflammatory invasion and microbiome imbalance. The online version contains supplementary material available at 10.1186/s13099-021-00447-z.
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DOI：
10.15252/embj.201797537
发表时间：
2018-03-01
期刊：
The EMBO journal
影响因子：
--
作者：
Sáez de Guinoa J;Jimeno R;Gaya M;Kipling D;Garzón MJ;Dunn-Walters D;Ubeda C;Barral P
通讯作者：
Barral P
影响因子：
3.7
作者：
Devine AA;Gonzalez A;Speck KE;Knight R;Helmrath M;Lund PK;Azcarate-Peril MA
通讯作者：
Azcarate-Peril MA
影响因子：
4.1
作者：
Frosali S;Pagliari D;Gambassi G;Landolfi R;Pandolfi F;Cianci R
通讯作者：
Cianci R
DOI：
10.1038/nri2335
发表时间：
2008-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM