MicroRNAs (miRNAs) are an emerging group of short, noncoding RNAs that play an important role in regulating expression of classical genes. Thus far little is known about their role in autoimmune demyelination. In this study, we analyzed changes in the miRNA profile in CD4 + T cells that occurred during the recognition of the myelin autoantigen, MOG . We found that, both in vivo and in vitro, myelin antigen stimulation resulted in significant up-regulation of miR-301a, miR-21, and miR-155. Furthermore, these three miRNAs were overexpressed in T cells infiltrating the CNS in animals with experimental autoimmune encephalomyelitis. Use of specific miRNA antagonists, antagomirs, revealed that miR-301a contributed to the development of the T-helper type 17 subset via targeting the IL-6/23-STAT3 pathway. This contribution appeared to be mediated by the miR-301a effect on the expression of the PIAS3, a potent inhibitor of the STAT3 pathway. Manipulation of miR-301a levels or PIAS3 expression in myelin-specific CD4 + T cells led to significant changes in the severity of experimental autoimmune encephalomyelitis. Thus, we have identified a role of miR-301a in regulating the function of myelinreactive T-helper type 17 cells, supporting a role for miR-301a and PIAS3 as candidates for therapeutic targets for controlling of autoimmune demyelination.M ultiple sclerosis (MS) is an organ-specific autoimmune disease manifested by chronic inflammatory demyelination of the CNS. CD4 + T-cell-mediated autoimmunity, with a critical role of a putative myelin autoantigen, has long been accepted as one of the most important aspects of MS pathogenesis, especially for the early initiation of disease (1). This understanding has been particularly complemented by the research on the MS animal model, experimental autoimmune encephalomyelitis (EAE). T-helper type 1 (Th1) cells, characterized by the expression of the transcription factor T-bet and the production of IFN-γ, originally were considered the major effector T-helper cells that mediate the pathogenesis of autoimmune demyelination (2). More recently another subset of T-helper cells, Th17, characterized by expression of the transcription factors retinoic acid receptor-related orphan receptor alpha (ROR-α) and retinoic acid receptor-related orphan receptor gamma t (ROR-γt) and by the production of IL-17, has been considered pivotal for the propagation of autoimmune demyelination (3). Mice with impaired numbers or function of Th17 cells, particularly mice deficient in the cytokines IL-6 or IL-23, are largely resistant to EAE (4-6). However, precise mechanisms governing the development and function of Th17 cells resulting in autoimmune demyelination are still unclear. Thus, Th17-targeting therapeutic approaches for MS have not yet been established.MicroRNAs (miRNAs) have begun to emerge as an important component in the differentiation and function of cells involved in the immune response. miRNAs operate as noncoding RNA molecules ∼22 nt in length that are processed from larger transcripts o...

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Background: Hemophagocytic lymphohistiocytosis (HLH) is a rarely recognized hyperinflammatory condition of high death risk. Objective: The objective was to describe a case of HLH in a patient with multiple sclerosis (MS) treated with ocrelizumab Methods: Clinical observation, laboratory testing, and use of HLH-2004 criteria for HLH diagnosis. Results: A 32-year-old Caucasian female developed HLH during ocrelizumab treatment. She met six of the eight HLH criteria including fever, splenomegaly, cytopenia, hypertriglyceridemia and hypofibrinogenemia, high serum ferritin level, and low natural killer (NK) cells. Conclusion: HLH should be considered in the differential diagnosis in MS patients displaying a fever and malaise syndrome following administration of ocrelizumab.