(DOC) PRISMA Flow Diagram S1 (DOC)  Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4(+) T cells form the core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4(+) T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4(+) T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper. Multiple sclerosis (MS) was initially identified in 1868 by Charcot. This disease often begins in young adulthood with intermittent episodes of neurological dysfunction, including visual impairment, ataxia, motor and sensory deficits, and bowel and bladder incontinence. These are attributable to recurrent inflammatory attacks on the white matter of the brain and spinal cord, which lead to the accumulation of perivascularly distributed inflammatory cells within the brain and spinal cord white matter [1] . Beeton et al. first established an animal model of MS in the 1930s, when they immunized monkeys with a central nervous system (CNS) homogenate to induce what is now known as experimental autoimmune encephalomyelitis (EAE) [2] . Since this pilot animal study, EAE has become the most accepted animal model of MS. In recent decades, pathogenic hypotheses have been investigated and novel therapeutic agents tested in this model in the fields of CNS inflammation and demyelination. Therefore, EAE provides a valuable tool for the investigation of the T-cell-dependent pathogenesis of autoimmune inflammation in the CNS and the orchestration of the autoimmune demyelinating inflammation in the CNS of MS patients. Mice and/or genetically modified mice have also been of fundamental value in the exploration of the complex pathogenesis of MS [3, 4] . EAE is undoubtedly the best animal model in which to study autoimmune diseases and particularly the demyelinating diseases of the CNS, such as MS [5] .