JCI - Anti–IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

Anti–IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

Yi Chen, Claire L. Langrish, Brent Mckenzie, Barbara Joyce-Shaikh, Jason S. Stumhofer, Terrill McClanahan, Wendy Blumenschein, Tatyana Churakovsa, Justin Low, Leonard Presta, Christopher A. Hunter, Robert A. Kastelein, Daniel J. Cua

Published in Volume 116, Issue 5

J Clin Invest. 2006; 116(5):1317–1326 doi:10.1172/JCI25308

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Figure 3

Anti–IL-23p19 mAbs inhibit CNS infiltration of IL-17–, IFN-γ– and TNF-producing CD4⁺ T cells.

The total number of CD4⁺ T cells, CD45^hiCD11b⁺ macrophages, and CD45^loCD11b⁺ microglia in the brain and spinal cord of antibody-treated mice was determined by FACS analysis. CNS mononuclear cells were isolated either (A) 2 days before expected EAE onset or (B) 2 days after disease onset. (C) Intracellular expression of IL-17 and IFN-γ in CD4⁺ T cells isolated from the CNS at peak disease. IL-17 and IFN-γ production by CD4⁺ CNS-infiltrating cells were determined following immediate ex vivo stimulation with PMA/ionomycin for 4 hours prior to intracellular cytokine analysis. Data are representative of 2 independent experiments. (D) Cells isolated from the brains and spinal cords of 3 mice were pooled for intracellular cytokine analysis. Data are the average number of IL-17–, IFN-γ–, and TNF-producing CNS-infiltrating T cells per animal. All cell samples were stimulated with PMA/ionomycin for 4 hours prior to analysis. All plots were gated on live CD4⁺ T cells and are representative of 2 independent experiments.