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Lauren Cohn

Bio: Lauren Cohn is an academic researcher from Yale University. The author has contributed to research in topics: Inflammation & Asthma. The author has an hindex of 36, co-authored 71 publications receiving 9407 citations.
Topics: Inflammation, Asthma, Mucus, Cytokine, Eosinophilia


Papers
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Journal ArticleDOI
TL;DR: Human and animal data are reviewed detailing the cellular and molecular interactions in established allergic asthma that promote persistent disease, amplify inflammation, and, in turn, cause disease progression.
Abstract: ▪ Abstract When asthma is diagnosed, eosinophilic inflammation and airway remodeling are established in the bronchial airways and can no longer be separated as cause and effect because both processes contribute to persistence and progression of disease, despite anti-inflammatory therapy. Th2 cells are continually active in the airways, even when disease is quiescent. IL-13 is the key effector cytokine in asthma and stimulates airway fibrosis through the action of matrix metalloproteinases on TGF-β and promotes epithelial damage, mucus production, and eosinophilia. The production of IL-13 and other Th2 cytokines by non-T cells augments the inflammatory response. Inflammation is amplified by local responses of the epithelium, smooth muscle, and fibroblasts through the production of chemokines, cytokines, and proteases. Injured cells produce adenosine that enhances IL-13 production. We review human and animal data detailing the cellular and molecular interactions in established allergic asthma that promote p...

856 citations

Journal ArticleDOI
11 Jun 2004-Science
TL;DR: It is shown that acidic mammalian chitinase (AMCase) is induced via a T helper-2 (Th2)–specific, interleukin-13 (IL-13)–mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma.
Abstract: Chitin is a surface component of parasites and insects, and chitinases are induced in lower life forms during infections with these agents. Although chitin itself does not exist in humans, chitinases are present in the human genome. We show here that acidic mammalian chitinase (AMCase) is induced via a T helper-2 (Th2)-specific, interleukin-13 (IL-13)-mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma. AMCase neutralization ameliorated Th2 inflammation and airway hyperresponsiveness, in part by inhibiting IL-13 pathway activation and chemokine induction. AMCase may thus be an important mediator of IL-13-induced responses in Th2-dominated disorders such as asthma.

795 citations

Journal ArticleDOI
Dong-Hong Zhang1, Lauren Cohn1, Prabir Ray1, Kim Bottomly1, Anuradha Ray1 
TL;DR: It is demonstrated that GATA-3 is critical for expression of the IL-5 gene in bona fide Th2 cells and has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases.

684 citations

Journal ArticleDOI
05 Apr 2002-Science
TL;DR: CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at the site of tissue injury, and impaired activation of transforming growth factor–β1.
Abstract: Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at the site of tissue injury, and impaired activation of transforming growth factor-beta1. This phenotype was partially reversed by reconstitution with CD44+ cells, thus demonstrating a critical role for this receptor in resolving lung inflammation.

673 citations

Journal ArticleDOI
TL;DR: VEGF is a mediator of vascular and extravascular remodeling and inflammation that enhances antigen sensitization and is crucial in adaptive TH2 inflammation and VEGF regulation may be therapeutic in asthma and other TH2 disorders.
Abstract: Exaggerated levels of VEGF (vascular endothelial growth factor) are present in persons with asthma, but the role(s) of VEGF in normal and asthmatic lungs has not been defined. We generated lung-targeted VEGF165 transgenic mice and evaluated the role of VEGF in T-helper type 2 cell (TH2)-mediated inflammation. In these mice, VEGF induced, through IL-13–dependent and –independent pathways, an asthma-like phenotype with inflammation, parenchymal and vascular remodeling, edema, mucus metaplasia, myocyte hyperplasia and airway hyper-responsiveness. VEGF also enhanced respiratory antigen sensitization and TH2 inflammation and increased the number of activated DC2 dendritic cells. In antigen-induced inflammation, VEGF was produced by epithelial cells and preferentially by TH2 versus TH1 cells. In this setting, it had a critical role in TH2 inflammation, cytokine production and physiologic dysregulation. Thus, VEGF is a mediator of vascular and extravascular remodeling and inflammation that enhances antigen sensitization and is crucial in adaptive TH2 inflammation. VEGF regulation may be therapeutic in asthma and other TH2 disorders.

566 citations


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Journal ArticleDOI
TL;DR: This Review suggests a new grouping of macrophages based on three different homeostatic activities — host defence, wound healing and immune regulation, and proposes that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation.
Abstract: Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.

7,384 citations

Journal ArticleDOI
TL;DR: The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for Macrophage-centered diagnostic and therapeutic strategies.
Abstract: Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.

4,721 citations

01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: This review will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-σB inhibition.
Abstract: The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.

4,110 citations

Journal ArticleDOI
22 Nov 1999-Oncogene
TL;DR: It is argued that NF-κB functions more generally as a central regulator of stress responses and pairing stress responsiveness and anti-apoptotic pathways through the use of a common transcription factor may result in increased cell survival following stress insults.
Abstract: Sixteen years have passed since the description of the nuclear factor-кB (NF-кB) as a regulator of к light-chain gene expression in murine B lymphocytes (Sen & Baltimore, 1986a) During that time, over 4,000 publications have appeared, characterizing the family of Rel/NF-кB transcription factors involved in the control of a large number of normal and pathological cellular processes The physiological functions of NF-кB proteins include immunological and inflammatory responses, developmental processes, cellular growth and modulating effects on apoptosis In addition, these factors are activated in a number of diseases, including cancer, arthritis, acute and chronic inflammatory states, asthma, as well as neurodegenerative and heart diseases

3,728 citations