Therapeutic Targeting of STAT pathways in CNS autoimmune diseases

Molecular Immunology Section
JAK-STAT 09/2013; 2(1):e24134. DOI: 10.4161/jkst.24134
Source: PubMed


Signal transducers and activators of transcription (STATs) transduce extracellular signals that regulate the initiation, duration and intensity of immune responses. However, unbridled activation of STATs by pro-inflammatory cytokines or growth factors contributes to pathogenic autoimmunity. In this review, we briefly discuss STAT pathways that promote the development and expansion of T cells that mediate two CNS inflammatory diseases, multiple sclerosis (MS) and uveitis. Particular focus is on animal models of MS and uveitis and new approaches to the treatment of CNS autoimmune diseases based on therapeutic targeting of Th17 cells and STAT pathways.

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Available from: Joseph Larkin, Jul 30, 2014
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    • "As mentioned previously, Th17 cells were found to be the central effector lineage involved in the pathogenicity of murine EAE, an important model of multiple sclerosis (MS) [11]. MS is a neurodegenerative autoimmune disorder in which axon demyelination lesions develop in the central nervous system (CNS) [90]. Prior to the discovery of Th17 cells, researchers had already begun to publish on the positive correlations found between levels of IL-17, IL-6, and G-CSF and the progression of active multiple sclerosis [152]. "
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    • "Treatment of SJL/J mice with SOCS1-KIR beginning 12 days post-immunization with myelin basic protein (MBP) resulted in minimal symptoms of EAE, while most control treated mice developed paraplegia (90). Th1 and Th17 cells via IFNγ and IL-17, respectively, are thought to play critical roles in the pathogenesis of EAE and multiple sclerosis (91). SOCS1-KIR treatment suppressed interleukin-17A (IL-17A) production by MBP-specific lymphocytes, as well as MBP-induced lymphocyte proliferation. "
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