期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms22073745
关键词
graft-vs-host disease; antibiotics; microbiome; dry eye disease; gentamicin
资金
- Japanese Ministry of Education, Science, Sports, Culture and Technology [18K09421, 20K18394]
- Japan Agency for Medical Research and Development [20he1022003h0001, 20hk0302008h0201, 20hk0302008h0101]
- Akaeda medical research foundation
- JST ERATO [JPMJER1902]
- AMED-CREST [JP20gm1010009]
- Takeda Science Foundation
- Food Science Institute Foundation
- Program for the Advancement of Research in Core Projects under Keio University's Longevity Initiative
- Grants-in-Aid for Scientific Research [20K18394, 18K09421] Funding Source: KAKEN
In this study, it was found in a mouse model that gentamicin (GM) significantly suppressed systemic cGVHD phenotypes and ocular manifestations, and reduced inflammatory cell infiltration and fibrosis in cGVHD-targeted organs. Although GM maintained higher levels of regulatory T cells, there were fewer Th17 cells and IL-6-producing macrophages in cGVHD-targeted organs. These findings suggest that orally administered GM may have positive effects in a cGVHD mouse model.
Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model.
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