Microbiology and Immunology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Int J Mol Sci. 2018 Oct 19;19(10):3241. doi: 10.3390/ijms19103241.
Gut commensal microorganisms have been linked with chronic inflammation at the extra-intestinal niche of the body. The object of the study was to investigate on the chronic effects of a gut commensal on extra-intestinal glands. The presence of autoimmune response was diagnosed by autoantibody levels and histological methods. Repeated injection of induced mononuclear cell inflammation in the Harderian and submandibular salivary glands of female C57BL/6 mice. Inflammation was reproduced by adoptive transfer of splenocytes to immune-deficient Rag2 knockout mice and CD4⁺ T cells to mature T cell-deficient TCRβ-TCRδ knockout mice. MALDI TOF mass spectrometry of the protein to which sera of -treated mice reacted was determined as the outer membrane protein A (OmpA) of . Multiple genera of the Enterobacteriaceae possessed OmpA with high amino-acid sequence similarities. Repeated injection of recombinant OmpA reproduced mononuclear cell inflammation of the Harderian and salivary glands in mice and elevation of autoantibodies against Sjögren's-syndrome-related antigens SSA/Ro and SSB/La. The results indicated the possibility of chronic stimuli from commensal bacteria-originated components as a pathogenic factor to elicit extra-intestinal autoimmunity.
肠道共生微生物与身体的肠外生态位的慢性炎症有关。本研究的目的是研究肠道共生菌对肠外腺体的慢性影响。通过自身抗体水平和组织学方法诊断自身免疫反应的存在。重复注射可诱导雌性 C57BL/6 小鼠哈德腺和颌下腺的单核细胞炎症。通过将脾细胞转移到免疫缺陷 Rag2 敲除小鼠和 CD4⁺T 细胞转移到成熟 T 细胞缺陷 TCRβ-TCRδ敲除小鼠中,重现了炎症。用 - 处理的小鼠的血清反应的蛋白质的 MALDI-TOF 质谱分析确定为 的外膜蛋白 A(OmpA)。肠杆菌科的多个属都具有与高氨基酸序列相似性的 OmpA。重复注射重组 OmpA 可在小鼠的哈德腺和唾液腺中重现单核细胞炎症,并升高针对干燥综合征相关抗原 SSA/Ro 和 SSB/La 的自身抗体。结果表明,来自共生细菌起源成分的慢性刺激可能是引发肠外自身免疫的致病因素。