Abstract：
:Mouse models have contributed to the bulk of knowledge on Systemic Lupus Erythematosus (SLE). Nevertheless, substantial differences exist between human and mouse immune system. We aimed to establish and characterise a SLE model mediated by human immune system. Injection of pristane into immunodeficient mice reconstituted with human immune system (humanised mice) recapitulated key SLE features, including: production of human anti-nuclear autoantibodies, lupus nephritis, and pulmonary serositis. There was a reduction in the number of human lymphocytes in peripheral blood, resembling lymphopenia in SLE patients. Concurrently, B cells and T cells were systemically hyperactivated, with a relative expansion of CD27+ and CD27-IgD- memory B cells, increased number of plasmablasts/plasma cells, and accumulation of effector memory T cells. There was also an increased production of human pro-inflammatory cytokines, including: IFN-γ, IL-8, IL-18, MCP-1, and IL-6, suggesting their role in SLE pathogenesis. Increased expression of type I IFN signature genes was also found in human hepatocytes. Altogether, we showed an SLE model that was mediated by human immune system, and which recapitulated key clinical and immunological SLE features. The advancements of humanised mice SLE model would provide an in vivo platform to facilitate translational studies and pre-clinical evaluations of human-specific mechanisms and immunotherapies.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Gunawan M,Her Z,Liu M,Tan SY,Chan XY,Tan WWS,Dharmaraaja S,Fan Y,Ong CB,Loh E,Chang KTE,Tan TC,Chan JKY,Chen Qdoi
10.1038/s41598-017-16999-7subject
Has Abstractpub_date
2017-11-30 00:00:00pages
16642issue
1issn
2045-2322pii
10.1038/s41598-017-16999-7journal_volume
7pub_type
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