Cutting edge: Nanogel-based delivery of an inhibitor of CaMK4 to CD41 T cells suppresses experimental autoimmune encephalomyelitis and lupus-like disease in mice

Kotaro Otomo, Tomohiro Koga, Masayuki Mizui, Nobuya Yoshida, Christina Kriegel, Sean Bickerton, Tarek M. Fahmy, George C. Tsokos

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5533-5537
Number of pages5
JournalJournal of Immunology
Volume195
Issue number12
DOIs
Publication statusPublished - 2015 Dec 15
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Autoimmune Diseases
T-Lymphocytes
Th17 Cells
Interleukin-17
Immunosuppressive Agents
Autoimmunity
Pharmaceutical Preparations
Interleukin-2
Cell Differentiation
Spinal Cord
Kidney
NanoGel

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cutting edge : Nanogel-based delivery of an inhibitor of CaMK4 to CD41 T cells suppresses experimental autoimmune encephalomyelitis and lupus-like disease in mice. / Otomo, Kotaro; Koga, Tomohiro; Mizui, Masayuki; Yoshida, Nobuya; Kriegel, Christina; Bickerton, Sean; Fahmy, Tarek M.; Tsokos, George C.

In: Journal of Immunology, Vol. 195, No. 12, 15.12.2015, p. 5533-5537.

Research output: Contribution to journalArticle

Otomo, Kotaro ; Koga, Tomohiro ; Mizui, Masayuki ; Yoshida, Nobuya ; Kriegel, Christina ; Bickerton, Sean ; Fahmy, Tarek M. ; Tsokos, George C. / Cutting edge : Nanogel-based delivery of an inhibitor of CaMK4 to CD41 T cells suppresses experimental autoimmune encephalomyelitis and lupus-like disease in mice. In: Journal of Immunology. 2015 ; Vol. 195, No. 12. pp. 5533-5537.
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