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

研究成果: Article

20 引用 (Scopus)

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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.

元の言語English
ページ(範囲)5533-5537
ページ数5
ジャーナルJournal of Immunology
195
発行部数12
DOI
出版物ステータスPublished - 2015 12 15
外部発表Yes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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