Format

Send to

Choose Destination
J Immunol. 2015 Dec 15;195(12):5533-7. doi: 10.4049/jimmunol.1501603. Epub 2015 Nov 11.

Cutting Edge: Nanogel-Based Delivery of an Inhibitor of CaMK4 to CD4+ T Cells Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice.

Author information

1
Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;
2
Department of Biomedical Engineering, Yale University and Yale University School of Medicine, New Haven, CT 06511;
3
Department of Biomedical Engineering, Yale University and Yale University School of Medicine, New Haven, CT 06511; Department of Chemical and Environmental Engineering, Yale University and Yale University School of Medicine, New Haven, CT 06511; and Department of Immunobiology, Yale University and Yale University School of Medicine, New Haven, CT 06511.
4
Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; gtsokos@bidmc.harvard.edu.

Abstract

Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4(+) T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models. The targeted delivery of KN93 did not deplete T cells but effectively blocked Th17 cell differentiation and expansion as measured in the spinal cords and kidneys of mice developing experimental autoimmune encephalomyelitis or lupus, respectively. These results highlight the promise of cell-targeted inhibition of molecules involved in the pathogenesis of autoimmunity as a means of advancing the treatment of autoimmune diseases.

PMID:
26561550
PMCID:
PMC4670795
DOI:
10.4049/jimmunol.1501603
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center