Temporal overexpression of IL-22 and Reg3γ differentially impacts the severity of experimental autoimmune encephalomyelitis.

IL-22 is an alpha-helical cytokine which belongs to the IL-10 family of cytokines. IL-22 is produced by RORγt+ innate and adaptive lymphocytes, including ILC3, γδ T, iNKT, Th17 and Th22 cells and some granulocytes. IL-22 receptor is expressed primarily by non-haematopoietic cells. IL-22 is critical for barrier immunity at the mucosal surfaces in the steady state and during infection. Although IL-22 knockout mice were previously shown to develop experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), how temporal IL-22 manipulation in adult mice would affect EAE course has not been studied previously. In this study, we overexpressed IL-22 via hydrodynamic gene delivery or blocked it via neutralizing antibodies in C57BL/6 mice to explore the therapeutic impact of IL-22 modulation on the EAE course. IL-22 overexpression significantly decreased EAE scores and demyelination, and reduced infiltration of IFN-γ+IL-17A+Th17 cells into the central nervous system (CNS). The neutralization of IL-22 did not alter the EAE pathology significantly. We show that IL-22-mediated protection is independent of Reg3γ, an epithelial cell-derived antimicrobial peptide induced by IL-22. Thus, overexpression of Reg3γ significantly exacerbated EAE scores, demyelination and infiltration of IFN-γ+IL-17A+ and IL-17A+GM-CSF+Th17 cells to CNS. We also show that Reg3γ may inhibit IL-2-mediated STAT5 signalling and impair expansion of Treg cells in vivo and in vitro. Finally, Reg3γ overexpression dramatically impacted intestinal microbiota during EAE. Our results provide novel insight into the role of IL-22 and IL-22-induced antimicrobial peptide Reg3γ in the pathogenesis of CNS inflammation in a murine model of MS.

Transient monocular visual impairment as an initial symptom of COVID-19 infection in an individual with multiple sclerosis receiving teriflunomide.

In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. Since the outbreak of the pandemic, in addition to the well-known COVID-19 symptoms, various neurological symptoms have been also described in patients with COVID-19. Here, we report an unusual presentation of COVID-19 infection in a teriflunomide-treated individual with multiple sclerosis (MS) who did not interrupt teriflunomide treatment during the infection. The course of the infection was mild in this case as in other reported teriflunomide-treated individuals with COVID-19. COVID-19's presentation may be unusual in people with MS (pwMS). It can also be concluded that teriflunomide may be considered a safe disease-modifying treatment option during the pandemic.

Incidence and Features of Acute Ischemic Stroke in Patients Hospitalized with COVID-19: A Multi-center Study in Turkey.

Introduction: Acute ischemic stroke (AIS) is a devastating complication of COVID-19 with high morbidity and mortality. In this study, we reported the frequency, characteristics, and outcome of AIS in patients with COVID-19. Methods: This multicenter and cross-sectional study was conducted between April 2020 and February 2021. Among the hospitalized patients with COVID-19, the detailed characteristics of those with and without AIS were recorded and compared. Results: Six hundred ninety-three patients were included in the study. Acute ischemic stroke was detected in 16 (2.31%) patients, the median age was 77 (range, 48-91) years, and 10 (62.5%) were female. The median NIHSS score at admission was 9 (range, 3-17). Total anterior circulation infarction (TACI) was the most common (37.5%) type and cardioembolism was the most common etiology (37.5%). Nine patients (56.25%) developed AIS within 24 hours of having COVID-19. COVID-19 severity was severe or critical in seven patients (43.75%). Eight patients died, and eight were discharged. Patients with AIS had a higher rate of hypertension, coronary artery disease, heart failure, a history of myocardial infarction, a history of cerebrovascular disease, severe and critical COVID-19, a higher mean age, and a longer ICU stay compared with those without AIS (p<0.001 for each). Conclusions: AIS can occur in patients with COVID-19 and is associated with mortality. Acute ischemic stroke is encountered at any stage of COVID-19, especially within the first 72 hours of the diagnosis, in older patients with comorbidities and severe COVID-19. There is an increased risk of AIS in patients with COVID-19 with a history of stroke.