A chimeric human-mouse model of Sjögren's syndrome

Nicholas A Young; Lai-Chu Wu; Michael Bruss; Benjamin H Kaffenberger; Jeffrey Hampton; Brad Bolon; Wael N Jarjour

doi:10.1016/j.clim.2014.10.004

A chimeric human-mouse model of Sjögren's syndrome

Clin Immunol. 2015 Jan;156(1):1-8. doi: 10.1016/j.clim.2014.10.004. Epub 2014 Oct 24.

Authors

Nicholas A Young¹, Lai-Chu Wu¹, Michael Bruss¹, Benjamin H Kaffenberger¹, Jeffrey Hampton¹, Brad Bolon², Wael N Jarjour³

Affiliations

¹ Division of Rheumatology and Immunology, The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
² Department of Veterinary Biosciences and the Comparative Pathology and Mouse Phenotyping Shared Resource, The Ohio State University, Columbus, OH 43210, USA; Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA.
³ Division of Rheumatology and Immunology, The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA. Electronic address: Wael.Jarjour@osumc.edu.

Abstract

Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology.

Keywords: Animal model; Chimera; Humanized mouse; Sjögren's syndrome.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chimera*
Disease Models, Animal*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Mice
Sjogren's Syndrome* / immunology

Abstract

Publication types

MeSH terms

Grants and funding