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Full-Text Articles in Life Sciences

Cellular Differentiation Of Human Monocytes Is Regulated By Time-Dependent Interleukin-4 Signaling And The Transcriptional Regulator Ncor2, Jil Sander, Eicke Latz, Andreas Schlitzer Dec 2017

Cellular Differentiation Of Human Monocytes Is Regulated By Time-Dependent Interleukin-4 Signaling And The Transcriptional Regulator Ncor2, Jil Sander, Eicke Latz, Andreas Schlitzer

Open Access Articles

Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic. We demonstrate that monocytes differentiated by macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) resembled in vivo inflammatory macrophages, while moDCs resembled in vivo inflammatory DCs. Moreover, differentiated monocytes presented with profound transcriptomic ...


Role Of Granulocyte-Macrophage Colony-Stimulating Factor Production By T Cells During Mycobacterium Tuberculosis Infection, Alissa C. Rothchild, Britni L. Stowell, Girija Goyal, Claudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M. Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M. Behar Oct 2017

Role Of Granulocyte-Macrophage Colony-Stimulating Factor Production By T Cells During Mycobacterium Tuberculosis Infection, Alissa C. Rothchild, Britni L. Stowell, Girija Goyal, Claudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M. Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M. Behar

UMass Metabolic Network Publications

Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF(-/-)) are highly susceptible to infection with Mycobacterium tuberculosis, and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T ...


Invitro-Q: A High-Throughput Biosensor Used To Evaluate The Mechanism Of Phagocytosis Of Macrophages Using Different Particles, Marynawal Abdou, Abiche H. Dewilde May 2017

Invitro-Q: A High-Throughput Biosensor Used To Evaluate The Mechanism Of Phagocytosis Of Macrophages Using Different Particles, Marynawal Abdou, Abiche H. Dewilde

UMass Center for Clinical and Translational Science Research Retreat

The method of phagocytosis of a particle can provide information on how macrophages respond to a detected particle. The response elicited varies based on the nature of the particle and in turn changes which receptor-mediated phagocytosis is initiated. We have developed a multi-well cell-based sensor that can monitor real-time biological changes in living cells, such as mass redistribution, and viscoelasticity. This system provides unique kinetic information regarding the phenotypic change in the cells post treatment. As a proof of principle study, we evaluate macrophage phagocytosis using three different particles: latex beads, Zymosan A, and Staphylococcus aureus. These studies show the ...


Macrophages Are Regulators Of Whole Body Metabolism: A Dissertation, Joseph C. Yawe Oct 2016

Macrophages Are Regulators Of Whole Body Metabolism: A Dissertation, Joseph C. Yawe

GSBS Dissertations and Theses

Obesity is the top risk factor for the development of type 2 diabetes mellitus in humans. Obese adipose tissue, particularly visceral depots, exhibits an increase in macrophage accumulation and is described as being in a state of chronic low-grade inflammation. It is characterized by the increased expression and secretion of inflammatory cytokines produced by both macrophages and adipocytes, and is associated with the development of insulin resistance. Based on these observations, we investigated the potential role of macrophage infiltration on whole body metabolism, using genetic and diet-induced mouse models of obesity.

Using flow cytometry and immunofluorescence imaging we found that ...


Il-1 Signaling In Obesity-Induced Hepatic Lipogenesis And Steatosis, Kimberly A. Negrin, Rachel J. Roth Flach, Marina T. Distefano, Anouch Matevossian, Randall H. Friedline, Dae Young Jung, Jason K. Kim, Michael P. Czech Sep 2014

Il-1 Signaling In Obesity-Induced Hepatic Lipogenesis And Steatosis, Kimberly A. Negrin, Rachel J. Roth Flach, Marina T. Distefano, Anouch Matevossian, Randall H. Friedline, Dae Young Jung, Jason K. Kim, Michael P. Czech

Open Access Articles

Non-alcoholic fatty liver disease is prevalent in human obesity and type 2 diabetes, and is characterized by increases in both hepatic triglyceride accumulation (denoted as steatosis) and expression of pro-inflammatory cytokines such as IL-1beta. We report here that the development of hepatic steatosis requires IL-1 signaling, which upregulates Fatty acid synthase to promote hepatic lipogenesis. Using clodronate liposomes to selectively deplete liver Kupffer cells in ob/ob mice, we observed remarkable amelioration of obesity-induced hepatic steatosis and reductions in liver weight, triglyceride content and lipogenic enzyme expressions. Similar results were obtained with diet-induced obese mice, although visceral adipose tissue macrophage ...


Complex Roles Of Macrophages In Lipid Metabolism And Metabolic Disease: A Dissertation, Kimberly A. Negrin Apr 2014

Complex Roles Of Macrophages In Lipid Metabolism And Metabolic Disease: A Dissertation, Kimberly A. Negrin

GSBS Dissertations and Theses

The worldwide prevalence of obesity and metabolic disease is increasing at an exponential rate and current projections provide no indication of relief. This growing burden of obesity-related metabolic disorders, including type 2 diabetes mellitus (T2DM), highlights the importance of identifying how lifestyle choices, genetics and physiology play a role in metabolic disease and place obese individuals at a greater risk for obesity-related complications including insulin resistance (IR). This increased risk of IR, which is characterized by a decreased response to insulin in peripheral tissues including adipose tissue (AT) and liver, is associated with a chronic, low grade inflammatory state; however ...


Local Macrophage Proliferation In Adipose Tissue Is A Characteristic Of Obesity-Associated Inflammation: A Dissertation, Shinya U. Amano Mar 2013

Local Macrophage Proliferation In Adipose Tissue Is A Characteristic Of Obesity-Associated Inflammation: A Dissertation, Shinya U. Amano

GSBS Dissertations and Theses

Obesity and diabetes are major public health problems facing the world today. Extending our understanding of adipose tissue biology, and how it changes in obesity, will hopefully better equip our society in dealing with the obesity epidemic. Macrophages and other immune cells accumulate in the adipose tissue in obesity and secrete cytokines that can promote insulin resistance. Adipose tissue macrophages (ATMs) are thought to originate from bone marrow-derived monocytes, which infiltrate the tissue from the circulation. Much work has been done to demonstrate that inhibition of monocyte recruitment to the adipose tissue can ameliorate insulin resistance. While monocytes can enter ...