Medicine and Health Sciences Commons^™

Using Pet Imaging To Track Sting-Induced Interferon Signaling, Enitome E. Bafor, Howard A. Young

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In the 19th century, Ilya Metchnikoff defined and broadened our initial understanding of phagocytosis and, in 1908, went on to show that a cellular component (i.e., DNA) stimulates immune responses (1). About a century later, Janeway conceptualized pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) (2). Since then, we know that PAMP recognition by innate immune cells via PRRs activates the production of several cytokines, including interferons (IFNs), with the eventual recruitment of lymphocytes. Subsequent research discovered that innate immune recognition of double-stranded DNA (dsDNA) triggers autoimmune diseases (3). However, before the discovery of dsDNA sensors, an endoplasmic reticulum …

Cytokines: From Clinical Significance To Quantification, Chao Liu, Dewei Chu, Kourosh Kalantar-Zadeh, Jacob George, Howard A. Young, Guozhen Liu

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Cytokines are critical mediators that oversee and regulate immune and inflammatory responses via complex networks and serve as biomarkers for many diseases. Quantification of cytokines has significant value in both clinical medicine and biology as the levels provide insights into physiological and pathological processes and can be used to aid diagnosis and treatment. Cytokines and their clinical significance are introduced from the perspective of their pro- and anti-inflammatory effects. Factors affecting cytokines quantification in biological fluids, native levels in different body fluids, sample processing and storage conditions, sensitivity to freeze-thaw, and soluble cytokine receptors are discussed. In addition, recent advances …

Promise And Complexity Of Lupus Mouse Models, Erica Moore, Joshua A. Reynolds, Anne Davidson, Stefania Gallucci, Laurence Morel, Deepak A. Rao, Howard A. Young, Chaim Putterman

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As a follow up to a 2010 meeting deliberating on the benefits of studying mouse models of systemic lupus erythematosus (SLE), the virtual conference “Mouse models of lupus 10 years later” convened on 10 December 2020 to address a challenging decade that saw few new therapies approved, despite leaps in knowledge

Abnormalities in both innate and adaptive immunity characterize SLE, a systemic autoimmune disease with potentially severe consequences in patients. Treatment has traditionally been limited to broad-acting, side-effect-heavy immunosuppressants, which are also incompletely effective. Thus, the need for specific therapies targeting the pathogenic mechanisms of SLE remains unmet. Affirming the …

The Experts Speak: A New Feature In The Jicr, Michael Gale, Ram Savan, Adolfo Garcia-Sastre, Ludmila Prokunina-Olsso, Kuppusamy Balamurugan, Howard A. Young

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This month we launch a new feature in the JICR: The Experts Speak. This feature is designed to provide first-hand insight from topical experts in the fields of interferon, cytokines, innate immunity, and adaptive immune actions of cytokine biology in disease. We start by asking experts to comment on interferon, cytokines, and SARS-CoV-2.

Lessons Learned: New Insights On The Role Of Cytokines In Covid-19, Maja Buszko, Aleksandra Nita-Lazar, Jung Hyun Park, Pamela L. Schwartzberg, Daniela Verthelyi, Howard A. Young, Amy S. Rosenberg

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In the midst of resurging COVID-19 cases, the second NIH/FDA virtual COVID-19 and Cytokines symposium was held on 1 December 2020, focusing on longitudinal studies of COVID-19 immunity, including long-term consequences, potential associations with autoimmunity and the multisystem inflammatory syndrome in children (MIS-C).

A central and ongoing quest in COVID-19 research is to establish why and how SARS-CoV-2 elicits heterogeneity in disease severity and immunopathology among infected individuals. Hence, much effort has been exerted to understand the cellular basis of SARS-CoV-2-induced immune responses, with the aim of identifying new biomarkers and prognostic tools and developing new therapeutic options. Cytokines emerged …

Discussion Of “Is Group Testing Ready For Prime-Time In Disease Identification?” By Haber, Malinovsky, And Albert, Statistics In Medicine, 2021, Brad J. Biggerstaff

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I congratulate the authors on an interesting, instructive, and timely paper. Certainly, including the testing for SARS-CoV-2 example in a paper on a topic—group testing—of wide interest during the current COVID-19 pandemic emphasizes the relevance of the topic in public health and diagnostic medicine generally. But the thoughtful inclusion of the remaining examples—HIV, HPV, and cancer biomarker detection—illustrates that the issues considered are important even in less urgent times. In this note of discussion I will comment on two particular aspects in the paper that I found particularly informative, and then I will comment on two other, related areas that …

Ifnγ Is A Key Link Between Obesity And Th1-Mediated Autoimmune Diseases, Heekyong R. Bae, Myung-Sook Choi, Suntae Kim, Howard A. Young, M E. Gershwin, Seon Min Jeon, Eun Young Kwon

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Obesity, a characteristic of metabolic syndrome, is also associated with chronic inflammation and the development of autoimmune diseases. However, the relationship between obesity and autoimmune diseases remains to be investigated in depth. Here, we compared hepatic gene expression profiles among high-fat diet (HFD) mice using the primary biliary cholangitis (PBC) mouse model based on the chronic expression of interferon gamma (IFNγ) (ARE-Del-/- mice). The top differentially expressed genes affected by upstream transcriptional regulators IFNγ, LPS, and TNFα displayed an overlap in HFD and ARE-Del-/- mice, indicating that obesity-induced liver inflammation may be dependent on signaling via IFNγ. The top pathways …

Natural Killer Cell Transcript 4 Promotes The Development Of Sjӧgren's Syndrome Via Activation Of Rap1 On B Cells, Peng Qu, Todd Wuest, Yongfen Min, Ilias Alevizos, Howard A. Young, P. Charles Lin

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Autoimmune disorders are the third most common diseases in the United States, and affect the daily lives of millions of people. In this study, we analyzed patient samples, utilized a transgenic mouse model and human B cells to reveal Natural Killer Cell Transcript 4 (NK4) as a novel regulator that promotes the development of autoimmune disorders. NK4 was significantly elevated in samples from patients with Sjӧgren's Syndrome (SS). SS patients show elevated NK4 levels. There is a strong and positive correlation between the increased levels of NK4 and the duration of SS. Interestingly, transgenic expression of NK4 in a mouse …