Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS). EAE pathogenesis involves various cell types, cytokines, chemokines, and adhesion molecules. Given the complexity of the inflammatory response in EAE, it is likely that many immune mediators still remain to be discovered. To identify novel immune mediators of EAE pathogenesis, we performed an Affymetrix gene array screen on the spinal cords of mice at the onset stage of disease. This screening identified the gene encoding lipocalin 2 (Lcn2) as being significantly upregulated. Lcn2 is a multi-functional protein that plays a role in glial activation, matrix metalloproteinase (MMP) stabilization, and cellular iron flux. As many of these processes have been implicated in EAE, we characterized the expression and role of Lcn2 in this disease in C57BL/6 mice. We show that Lcn2 is significantly upregulated in the spinal cord throughout EAE and is expressed predominantly by monocytes and reactive astrocytes. The Lcn2 receptor, 24p3R, is also expressed on monocytes, macrophages/microglia, and astrocytes in EAE. In addition, we show that EAE severity is increased in Lcn2(-/-) mice as compared with wild-type controls. Finally, we demonstrate that elevated levels of Lcn2 are detected in the plasma and cerebrospinal fluid (CSF) in MS and in immune cells in CNS lesions in MS tissue sections. These data indicate that Lcn2 is a modulator of EAE pathogenesis and suggest that it may also play a role in MS.
Since the onset of the COVID-19 pandemic in the fall of 2019 over 4 million people have been infected and over 280,000 have died (1). Information about the SARS-CoV2 virus is evolving rapidly. At this time there are no interventions proven to be effective for cases infected with SARS-CoV2. Current knowledge about the clinical and laboratory manifestations of COVID-19 infection is reviewed and combined with knowledge about the immunopathogenic mechanisms of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV1) and Middle East Respiratory Syndrome (MERS) to formulate theories and suggest possible therapeutic interventions. SARS-CoV2 immunopathogenic mechanisms vary from immunosuppression that initially enables viral escape to a hyperinflammatory immune response. Ultimately therapeutic intervention will be phase dependent.
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