ICOS deficiency results in exacerbated IL-17 mediated experimental autoimmune encephalomyelitis
G Galicia, A Kasran, C Uyttenhove, K De Swert… - Journal of clinical …, 2009 - Springer
G Galicia, A Kasran, C Uyttenhove, K De Swert, J Van Snick, JL Ceuppens
Journal of clinical immunology, 2009•SpringerIntroduction Inducible costimulatory molecule (ICOS) is important for the effector function of T
cells, especially for Th2 and T cell dependent B cell responses. However, it has been shown
that ICOS is required for the differentiation of Th17 cells. Since IL-17 has been identified as a
major cytokine involved in the pathogenesis of experimental autoimmune encephalomyelitis
(EAE), the enhanced severity of EAE in ICOS-deficient mice (ICOS−/−) mice is unexpected.
Methods To better understand the role of ICOS and of IL-17 in EAE, we induced EAE in …
cells, especially for Th2 and T cell dependent B cell responses. However, it has been shown
that ICOS is required for the differentiation of Th17 cells. Since IL-17 has been identified as a
major cytokine involved in the pathogenesis of experimental autoimmune encephalomyelitis
(EAE), the enhanced severity of EAE in ICOS-deficient mice (ICOS−/−) mice is unexpected.
Methods To better understand the role of ICOS and of IL-17 in EAE, we induced EAE in …
Introduction
Inducible costimulatory molecule (ICOS) is important for the effector function of T cells, especially for Th2 and T cell dependent B cell responses. However, it has been shown that ICOS is required for the differentiation of Th17 cells. Since IL-17 has been identified as a major cytokine involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the enhanced severity of EAE in ICOS-deficient mice (ICOS−/−) mice is unexpected.
Methods
To better understand the role of ICOS and of IL-17 in EAE, we induced EAE in ICOS−/− by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35–55) in complete Freund’s adjuvant.
Results
As previously reported, we found that ICOS−/− mice developed more severe EAE. Upon restimulation with MOG35–55, splenocytes from ICOS−/− mice with EAE produced higher amounts of IL-17 and ICOS−/− mice had a higher expression of IL-17, IL-6, and TGF-β mRNA in the spinal cords at the onset of the disease. Finally, the blockade of IL-17 strongly inhibited disease even in ICOS−/− mice, showing that IL-17 is playing a major role in the pathogenesis of EAE both in WT and ICOS−/− mice.
Conclusion
In conclusion, MOG immunization induces MOG-specific Th17 cells also in ICOS−/− mice, and a higher expression of IL-17 and of Th17-driving cytokines IL-6 and TGF-β in the central nervous system at the onset of EAE that correlates with their more severe disease.
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