Machado Melissa S G, Rodrigues Vanessa F, Barbosa Sara C, Elias-Oliveira Jefferson, Pereira Ítalo S, Pereira Jéssica A, Pacheco Thaílla C F, Carlos Daniela
Laboratory of Immunoregulation of Metabolic Disease, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Microorganisms. 2024 Aug 20;12(8):1717. doi: 10.3390/microorganisms12081717.
Intestinal permeability and bacterial translocation are increased in obesity and metabolic syndrome (MS). ILC3 cells contribute to the integrity of intestinal epithelium by producing IL-22 via IL-1β and IL-23. This study investigates the role of IL-1R1 in inducing ILC3 cells and conferring protection during obesity and MS. For this purpose, C57BL/6 wild-type (WT) and IL-1R1-deficient mice were fed a standard diet (SD) or high-fat diet (HFD) for 16 weeks. Weight and blood glucose levels were monitored, and adipose tissue and blood samples were collected to evaluate obesity and metabolic parameters. The small intestine was collected to assess immunological and junction protein parameters through flow cytometry and RT-PCR, respectively. The intestinal permeability was analyzed using the FITC-dextran assay. The composition of the gut microbiota was also analyzed by qPCR. We found that IL-1R1 deficiency exacerbates MS in HFD-fed mice, increasing body fat and promoting glucose intolerance. A worsening of MS in IL-1R1-deficient mice was associated with a reduction in the ILC3 population in the small intestine. In addition, we found decreased IL-22 expression, increased intestinal permeability and bacterial translocation to the visceral adipose tissue of these mice compared to WT mice. Thus, the IL-1R1 receptor plays a critical role in controlling intestinal homeostasis and obesity-induced MS, possibly through the differentiation or activation of IL-22-secreting ILC3s.
肥胖和代谢综合征（MS）中肠道通透性和细菌易位增加。3型固有淋巴细胞（ILC3）通过经由白细胞介素-1β（IL-1β）和白细胞介素-23（IL-23）产生白细胞介素-22（IL-22）来维持肠道上皮的完整性。本研究调查白细胞介素-1受体1（IL-1R1）在肥胖和MS期间诱导ILC3细胞及提供保护作用中的角色。为此，给C57BL/6野生型（WT）和IL-1R1缺陷型小鼠喂食标准饮食（SD）或高脂饮食（HFD）16周。监测体重和血糖水平，并收集脂肪组织和血液样本以评估肥胖和代谢参数。收集小肠，分别通过流式细胞术和逆转录-聚合酶链反应（RT-PCR）评估免疫和连接蛋白参数。使用异硫氰酸荧光素-葡聚糖（FITC-葡聚糖）测定法分析肠道通透性。还通过定量聚合酶链反应（qPCR）分析肠道微生物群的组成。我们发现，IL-1R1缺陷会加剧高脂饮食喂养小鼠的MS，增加体脂并促进葡萄糖不耐受。IL-1R1缺陷型小鼠MS的恶化与小肠中ILC3细胞群的减少有关。此外，我们发现与WT小鼠相比，这些小鼠的IL-22表达降低、肠道通透性增加且细菌易位至内脏脂肪组织。因此，IL-1R1受体可能通过分泌IL-22的ILC3细胞的分化或激活，在控制肠道稳态和肥胖诱导的MS中起关键作用。
