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Lin J.,University of South Florida | Lwin T.,University of South Florida | Zhao J.-J.,University of South Florida | Tam W.,Cornell University | And 6 more authors.
Leukemia | Year: 2011

B-cell lymphoma 6 (BCL6) and PR domain containing 1 (PRDM1) are considered as master regulators for germinal center (GC) formation and terminal B-cell differentiation. Dysregulation of BCL6 and PRDM1 has been associated with lymphomagenesis. Here, we show for the first time that direct cell-cell contact between follicular dendritic cells (FDC) and B-lymphocytes, by influencing the expression of a set of microRNAs (miRNAs), regulates the expression of BCL6 and PRDM1. We identify that, on cell adhesion to FDC, FDC induces upregulation of PRDM1 expression through downregulation of miR-9 and let-7 families and induces downregulation of BCL-6 through upregulation of miR-30 family in B-lymphocytes and lymphoma cells. We further demonstrate that the miR-30 family directly controls BCL-6 expression and miR-9-1 and let-7a directly control PRDM-1 expression through targeting their 3′UTR, mediating the FDC effect. Our studies define a novel regulatory mechanism in which the FDC, through induction of miRNAs in B-lymphocytes, orchestrates the regulation of transcription factors, promotes germinal center B-cell survival and differentiation. Dysregulation of miRNAs may interfere with B-cell survival and maturation, thus representing a novel molecular mechanism, as well as a potential therapeutic target in B-cell lymphomas. © 2011 Macmillan Publishers Limited All rights reserved.

Lwin T.,University of South Florida | Lin J.,University of South Florida | Choi Y.S.,Laboratory of Cellular Immunology | Zhang X.,University of South Florida | And 5 more authors.
Blood | Year: 2010

Follicular dendritic cells (FDCs), an essential component of the lymph node microenvironment, regulate and support Blymphocyte differentiation, survival, and lymphoma progression. Here, we demonstrate that adhesion of mantle cell lymphoma and other non-Hodgkin lymphoma cells to FDCs reduces cell apoptosis and is associated with decreased levels of the proapoptotic protein, Bim. Bim down-regulation is posttranscriptionally regulated via up-regulation of microRNA-181a (miR-181a). miR-181a overexpression decreases, whereas miR-181a inhibition increases Bim levels by directly targeting Bim. Furthermore, we found that cell adhesion-up-regulated miR-181a contributes to FDC-mediated cell survival through Bim down-regulation, implicating miR-181a as an upstream effector of the Bim-apoptosis signaling pathway. miR-181a inhibition and Bim u-pregulation significantly suppressed FDC-mediated protection against apoptosis in lymphoma cell lines and primary lymphoma cells. Thus, FDCs protect B-cell lymphoma cells against apoptosis, in part through activation of a miR-181a-dependent mechanism involving down-regulation of Bim expression. We demonstrate, for the first time, that cell-cell contact controls tumor cell survival and apoptosis via microRNA in mantle cell and other non-Hodgkin lymphomas. Regulation of microRNAs by B-cell-FDC interaction may support B-cell survival, representing a novel molecular mechanism for cell adhesion-mediated drug resistance and a potential therapeutic target in B-cell lymphomas. © 2010 by The American Society of Hematology.

Amadori M.,Laboratory of Cellular Immunology
The Innate Immune Response to Non-infectious Stressors: Human and Animal Models | Year: 2016

The Innate Immune Response to Non-infectious Stressors: Human and Animal Models highlights fundamental mechanisms of stress response and important findings on how the immune system is affected, and in turn affects such a response. In addition, this book covers the crucial link between stress response and energy metabolism, prompts a re-appraisal of some crucial issues, and helps to define research priorities in this fascinating, somehow elusive field of investigation. Provides insights into the fundamental homeostatic processes vis-à-vis stressors to help in investigation Illustrates the depicted tenets and how to offset them against established models of response to physical and psychotic stressors in both animals and humans Covers the crucial issue of the immune response to endocrine disruptors Includes immunological parameters as reporter system of environmental adaptation Provides many illustrative examples to foster reader understanding. © 2016 Elsevier Inc. All rights reserved.

Zanotti C.,Laboratory of Cellular Immunology | Amadori M.,Laboratory of Cellular Immunology
Biologicals | Year: 2015

Porcine Circovirus 2 (PCV2) is involved in porcine circovirus-associated disease, that causes great economic losses to the livestock industry worldwide. Vaccination against PCV2 proved to be very effective in reducing disease occurrence and it is currently performed on a large scale. Starting from a previous model concerning Foot-and Mouth Disease Virus antigens, we developed a rapid and simple method to quantify PCV2 whole virion particles in inactivated vaccines. This procedure, based on sucrose gradient analysis and fluorometric evaluation of viral genomic content, allows for a better standardization of the antigen payload in vaccine batches. It also provides a valid indication of virion integrity. Most important, such a method can be applied to whole virion vaccines regardless of the production procedures, thus enabling meaningful comparisons on a common basis. In a future batch consistency approach to PCV2 vaccine manufacture, our procedure represents a valuable tool to improve in-process controls and to guarantee conformity of the final product with passmarks for approval. This might have important repercussions in terms of reduced usage of animals for vaccine batch release, in the framework of the current 3Rs policy. © 2015 The International Alliance for Biological Standardization.

Trevisi E.,Catholic University of the Sacred Heart | Zecconi A.,University of Milan | Cogrossi S.,Catholic University of the Sacred Heart | Razzuoli E.,Laboratory of Cellular Immunology | And 2 more authors.
Research in Veterinary Science | Year: 2014

The need for antibiotic treatments in dairy cattle farms can be reduced by a combined intervention scheme based on: (1) timely clinical inspections, (2) the assessment of animal-based welfare parameters, and (3) the use of predictive laboratory tests. These can provide greater insight into environmental adaptation of dairy cows and define animals at risk of contracting disease. In the long-term, an improved disease control justifies the adoption of such a combined strategy. Many antibiotic treatments for chronic disease cases are often not justified with a cost/benefit analysis, because the repeated drug administration does not give rise to the expected outcome in terms of animal health. In particular, compared with untreated cases, antibiotics may not lead to greater cure rates for some forms of mastitis. Lastly, a substantial reduction of antibiotic usage in dairy farms can be achieved through the proper use of immunomodulators, aimed at increasing immunocompetence and disease resistance of cows. © 2014 Elsevier Ltd.

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