期刊
JOURNAL OF INFLAMMATION RESEARCH
卷 15, 期 -, 页码 4027-4045出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S354224
关键词
schistosomiasis; NKG2D; liver fibrosis; IFN-?; natural killer cells; T lymphocytes
类别
资金
- National Natural Science Foundation of China [81772221, 81672047]
- Fundamental Research Funds for the Central Universities (HUST) [2015QN147, 2017KFYXJJ056]
- Natural Science Foundation of Hubei Province, China [2016CFB419]
- Foundation of Health and Family Planning Commission of Hubei Province, China [WJ2017X006]
This study provides the first in vivo evidence that MULT1 is a favorable anti-fibrosis factor in the context of schistosomiasis-associated hepatic fibrosis. By modulating the proportion and function of immune cells, MULT1 can improve the immune microenvironment affected by schistosomiasis infection and inhibit liver fibrosis.
Purpose: In schistosomiasis-associated hepatic fibrosis, the role of murine UL16-binding protein-like transcript 1 (MULT1), the strongest ligand of natural killer group 2-member D receptor (NKG2D), remains unclear. Here, Schistosoma japonicum-infected mice administered with MULT1-encoding DNA were used to test MULT1 as a potential therapy for schistosomiasis-associated hepatic fibrosis and explore relevant mechanisms. Materials and Methods: A recombinant plasmid encoding MULT1 (p-rMULT1) was constructed and administered to Schistosoma japonicum-infected BALB/c mice via hydrodynamic tail vein injection. Egg granulomas in liver, hepatic fibrosis biomarkers and levels of cytokines were investigated. Comparisons of CD4+ T, CD8+ T, NK and NKT proportions as well as their phenotype were performed not only between Schistosoma infected, p-rMULT1 treated group and Schistosoma infected, backbone plasmid pEGFP-N1 treated group but also between infected, nontreated group and health control group. Results: Reduced area of granuloma formation and fibrosis around single eggs, downregulated expression of collagen I, alpha-smooth muscle actin, TGF-beta and IL-10, and upregulated expression of IFN-gamma, were observed in the livers of p-rMULT1 treated mice. p-rMULT1 treatment improved Schistosoma infection impacted immune microenvironment by modulating proportion of CD4(+) T CD8(+) T, natural killer (NK) and NKT cells, enhancing expression of NKG2D, in lymphocytes, and augmenting IFN-gamma secretion by CD4(+)T, CD8(+) T, NK and NKT cells, as well as partially reversing some other phenotype changes of lymphocytes. Conclusion: To the best of our knowledge, we provided the first in vivo evidence that MULT1 is a favorable anti-fibrosis factor in the context of schistosomiasis. The inhibitory effect of MULT1 overexpression on schistosomiasis associated with hepatic fibrosis may result from augmenting the proportion and function of NKG2D-expressing immune cells, and from enhancing NK-and T-cell activation, as well as the T balance.
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