A Novel Human Systemic Lupus Erythematosus Model in Humanised Mice

@article{Gunawan2017ANH,
  title={A Novel Human Systemic Lupus Erythematosus Model in Humanised Mice},
  author={Merry Gunawan and Zhisheng Her and Min Liu and Sue Yee Tan and Xue Ying Chan and Wilson Wei Sheng Tan and Shubasree Dharmaraaja and Yong Fan and Chee Bing Ong and Eva Loh and Kenneth Tou En Chang and Thiam Chye Tan and Jerry Kok Yen Chan and Qingfeng Chen},
  journal={Scientific Reports},
  year={2017},
  volume={7}
}
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… 
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References

SHOWING 1-10 OF 59 REFERENCES
Transfer of human systemic lupus erythematosus in severe combined immunodeficient (SCID) mice
TLDR
It is concluded that human SLE serology and some associated renal changes can be reproduced solely by PBL transferred from afflicted patients, and that SCID-human-SLE mice may serve as an in vivo laboratory model for the study of human Sle.
Engraftment of peripheral blood mononuclear cells from systemic lupus erythematosus and antiphospholipid syndrome patient donors into BALB-RAG-2-/- IL-2Rγ-/- mice: a promising model for studying human disease.
TLDR
A humanized mouse model of systemic lupus erythematosus (SLE) that resembles the human disease in order to define the pathophysiology and targets for treatments is established and a novel humanized SLE-DKO mouse exhibiting many of the immunologic and clinical features of human SLE is established.
Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains
TLDR
The significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes.
Amelioration of lupus manifestations by a peptide based on the complementarity determining region 1 of an autoantibody in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes of systemic lupus erythematosus (SLE) patients
TLDR
Treatment with the hCDR1 peptide resulted in a significant amelioration of the clinical features manifested by proteinuria, human IgG complex deposits as well as deposits of murine complement C3, suggesting it is a potential candidate for a novel specific treatment of SLE patients.
The Pathology of T Cells in Systemic Lupus Erythematosus
TLDR
Current outcomes of clinical trials evaluating therapeutic agents which manipulate the T cells such as calcineurin inhibitors indicate that they are at least as efficacious and safe as conventional immunosuppressants in treating lupus glomerulonephritis, larger clinical trials are undoubtedly required to validate these as-yet favourable findings.
Murine Models of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder. The study of diverse mouse models of lupus has provided clues to the etiology of SLE. Spontaneous mouse models of lupus
Increase in activated CD8+ T lymphocytes expressing perforin and granzyme B correlates with disease activity in patients with systemic lupus erythematosus.
TLDR
A new and pivotal role of activated CD8+ T lymphocytes in SLE pathogenesis is disclosed as DCs generated in the presence of sera from SLE patients with active disease could promote the differentiation of CD8- effector T lymphocyte that are fully functional and able to generate SLE autoantigens.
T cells as therapeutic targets in SLE
TLDR
Biochemical characterization of SLE T cells has revealed distinct early and late signaling aberrations, and has enabled the identification of novel molecular targets that can be corrected with small molecules, and biomarkers that may foretell disease activity and predict organ damage.
Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus1
TLDR
It is concluded that myeloid DCs from SLE patients display significant changes in phenotype which promote aberrant T cell function and could contribute to the pathogenesis of SLE and organ damage.
Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus
TLDR
The correlation of raised plasma concentration and ex vivo production of inflammatory chemokines with disease activity, and their association with IL18, supports the view that chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE pathogenesis.
...
1
2
3
4
5
...