Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
NPJ Biofilms Microbiomes. 2020 Oct 30;6(1):49. doi: 10.1038/s41522-020-00158-4.
Mice lacking IκB-ζ, a protein encoded by the Nfkbiz gene, spontaneously develop a Sjögren's syndrome-like disease involving the lachrymal glands, but no salivary gland symptoms have been reported. We found that Nfkbiz female mice presented a significantly reduced salivary flow rate, focal lymphocytic sialadenitis (FLS), and a dysbiotic oral microbiota at week 24. To dissect the contributions of genetic and environmental factors to the salivary gland phenotype, Nfkbiz and Nfkbiz mice were cohoused after weaning and evaluated at week 20. Cohousing alleviated the salivary gland phenotype of Nfkbiz mice but did not induce any disease phenotype in Nfkbiz mice. Additionally, the oral microbiota in the cohoused mice was synchronized toward that in Nfkbiz mice. In conclusion, IκB-ζ-deficient mice developed hyposalivation and FLS, in which a dysbiotic oral microbiota played an important role. This finding suggests that the dysbiotic oral microbiota could be a therapeutic target.
缺乏 NFKBIZ 基因编码的蛋白 IκB-ζ的小鼠会自发出现类似于干燥综合征的疾病，涉及泪腺，但没有报道唾液腺症状。我们发现，NFKBIZ 雌性小鼠在第 24 周时唾液流量明显减少、出现局灶性淋巴细胞性唾液腺炎（FLS）和口腔微生物群落失调。为了剖析遗传和环境因素对唾液腺表型的贡献，我们在断奶后将 NFKBIZ 和 NFKBIZ 小鼠同笼饲养，并在第 20 周进行评估。同笼饲养减轻了 NFKBIZ 小鼠的唾液腺表型，但未在 NFKBIZ 小鼠中诱导任何疾病表型。此外，同笼饲养小鼠的口腔微生物群落向 NFKBIZ 小鼠的口腔微生物群落同步。总之，缺乏 IκB-ζ 的小鼠出现唾液分泌减少和 FLS，其中口腔微生物群落失调发挥了重要作用。这一发现提示口腔微生物群落失调可能是一个治疗靶点。
