Yan Song

Yale-New Haven Hospital, New Haven, Connecticut, United States

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Publications (3)19.75 Total impact

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    ABSTRACT: Infection with mosquito-borne West Nile virus (WNV) is usually asymptomatic but can lead to severe WNV encephalitis. The innate cytokine, macrophage migration inhibitory factor (MIF), is elevated in patients with WNV encephalitis and promotes viral neuroinvasion and mortality in animal models. In a case-control study, we examined functional polymorphisms in the MIF locus in a cohort of 454 North American patients with neuroinvasive WNV disease and found patients homozygous for high-expression MIF alleles to be >20-fold ( p= 0.008) more likely to have WNV encephalitis. These data indicate that MIF is an important determinant of severity of WNV neuropathogenesis and may be a therapeutic target.
    No preview · Article · Feb 2016 · Cytokine
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    ABSTRACT: Cardiac surgery involves myocardial ischemia/reperfusion (I/R) with potentially deleterious consequences. Macrophage migration inhibitory factor (MIF) is a stress-regulating chemokine-like cytokine that protects against I/R-damage, but functional links with its homolog D-dopachrome tautomerase (MIF-2) and the circulating soluble receptor CD74 (sCD74) are unknown. Here, we investigate the role of MIF, MIF-2, sCD74, and MIF genotypes in patients scheduled for elective single or complex surgical procedures such as coronary artery bypass-grafting or valve-replacement. MIF and MIF-2 levels significantly increased intra-operatively, whereas measured sCD74 decreased correspondingly. Circulating sCD74/MIF complexes were detectable in 50% of patients and enhanced MIF's antioxidant activity. Intra-operative MIF levels were independently associated with a reduced risk for the development of atrial fibrillation (AF) (odds-ratio 0.99 (0.98-1.00);p=0.007). Circulating levels of MIF-2, but not MIF, were associated with an increased frequency of organ-dysfunction and predicted the occurrence of AF (area-under-the-curve (AUC)=0.663;p=0.041) and pneumonia (AUC=0.708;p=0.040). Patients with a high-expression MIF-genotype exhibited a reduced incidence of organ-dysfunction compared to patients with low-expression MIF-genotypes (3 vs. 25;p=0.042). The current study comprehensively highlights the kinetics and clinical relevance of MIF family proteins and the MIF-genotype in cardiac surgery patients. Our findings suggest that increased MIF levels during cardiac surgery feature organ-protective properties during myocardial I/R, while the soluble MIF receptor sCD74 may enhance MIF's antioxidant activity. In contrast, high MIF-2 levels are predictive of the development of organ-dysfunction. Importantly, we provide first evidence for a gene-phenotype relationship between variant MIF-alleles and clinical outcome in cardiac surgery patients.
    Full-text · Article · Aug 2015 · Antioxidants & Redox Signaling
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    ABSTRACT: The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.
    Full-text · Article · Jul 2012 · Proceedings of the National Academy of Sciences