Zhou Yun, Hubscher Charles H
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, United States.
Kentucky Spinal Cord Injury Research Center, Louisville, KY, United States.
Immunohorizons. 2025 Feb 18;9(4). doi: 10.1093/immhor/vlaf002.
Neurogenic bowel dysfunction (NBD) is common after spinal cord injury (SCI). Gut-associated lymphoid tissue (GALT), an organized structure within the mucosal immune system, is important for the maintenance of gut homeostasis and body health and serves as the first line barrier/defense against diet antigens, commensal microbiota, pathogens, and toxins in mucosal areas. The current study examined gene expression levels along six segments of anorectal tissue using real-time polymerase chain reaction (RT-PCR) in uninjured rats (28-day sham surgical controls) and at both 28- and 42-days post-T9 contusion injury. Consistent with our previous report of functional regional differences in the ano-rectum, we demonstrate the existence of GALTs located primarily within the segment at 3-4.5 cm from the rectal dentate line (termed rectal GALTs-rGALTs) in shams with upregulated gene expression levels of multiple biomarkers, including B cell and T cell-related genes, major histocompatibility complex (MHC) class II molecules, and germinal center (GC)-related genes, which was further confirmed by histologic examination. In the same rectal tissue segment following T9 SCI, inflammation-related genes were upregulated at 28 days post-injury (DPI) indicating that microbial infection and inflammation of rGALTs modified structure and function of rGALTs, while at 42 DPI rGALTs exhibited resolution of inflammation and impaired structure/function for extrafollicular B cell responses. Taken together, our data suggest that rGALTs exists in rat rectum for homeostasis of gut microbiota/barrier. SCI induces microbial infection and inflammation in rectal tissues containing rGALTs, which could contribute to development of SCI-related gut microbiome dysbiosis, NBD, and systemic diseases.
神经源性肠道功能障碍(NBD)在脊髓损伤(SCI)后很常见。肠道相关淋巴组织(GALT)是黏膜免疫系统中的一种组织结构,对维持肠道内环境稳定和身体健康很重要,并且作为黏膜区域抵御饮食抗原、共生微生物群、病原体和毒素的第一道屏障/防线。本研究使用实时聚合酶链反应(RT-PCR)检测了未受伤大鼠(28天假手术对照组)以及T9挫伤损伤后28天和42天的肛门直肠组织六个节段的基因表达水平。与我们之前关于肛门直肠功能区域差异的报告一致,我们证明在假手术组中,主要位于距直肠齿状线3 - 4.5厘米节段内的GALT(称为直肠GALT - rGALT)存在,多种生物标志物的基因表达水平上调,包括B细胞和T细胞相关基因、主要组织相容性复合体(MHC)II类分子以及生发中心(GC)相关基因,组织学检查进一步证实了这一点。在T9脊髓损伤后的同一直肠组织节段中,损伤后28天(DPI)炎症相关基因上调,表明rGALT的微生物感染和炎症改变了rGALT的结构和功能,而在42 DPI时,rGALT表现出炎症消退以及滤泡外B细胞反应的结构/功能受损。综上所述,我们的数据表明rGALT存在于大鼠直肠中以维持肠道微生物群/屏障的内环境稳定。脊髓损伤会在含有rGALT的直肠组织中引发微生物感染和炎症,这可能导致脊髓损伤相关的肠道微生物群失调、神经源性肠道功能障碍和全身性疾病的发生。