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Gasteiger G.,Sloan Kettering Cancer Center | Gasteiger G.,University of Mainz Medical Center | Rudensky A.Y.,Sloan Kettering Cancer Center
Nature Reviews Immunology | Year: 2014

Innate lymphocytes-including natural killer cells and the recently discovered innate lymphoid cells-have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. The contribution of the adaptive immune system to the coordination of innate lymphocyte responses is less well understood. In this Opinion article, we review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which T cells of the adaptive immune system function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential roles of regulatory and helper T cells in these processes, and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. © 2014 Macmillan Publishers Limited. Source


Gasteiger G.,University of Mainz Medical Center | Ataide M.,University of Bonn | Kastenmuller W.,University of Bonn
Immunological Reviews | Year: 2016

The immune system is a multicentered organ that is characterized by intimate interactions between its cellular components to efficiently ward off invading pathogens. A key constituent of this organ system is the distinct migratory activity of its cellular elements. The lymph node represents a pivotal meeting point of immune cells where adaptive immunity is induced and regulated. Additionally, besides barrier tissues, the lymph node is a critical organ where invading pathogens need to be eliminated in order to prevent systemic distribution of virulent microbes. Here, we explain how the lymph node is structurally and functionally organized to fulfill these two critical functions - pathogen defense and orchestration of adaptive immunity. We will discuss spatio-temporal aspects of cellular immune responses focusing on CD8 T cells and review how and where these cells are activated in the context of viral infections, as well as how viral antigen expression kinetics and different antigen presentation pathways are involved. Finally, we will describe how such responses are regulated and 'helped', and discuss how this relates to intranodal positioning and cellular migration of the various cellular components that are involved in these processes. © 2016 John Wiley & Sons A/S. Source


Mehal W.Z.,Yale University | Mehal W.Z.,West Haven Veterans Medical Center | Schuppan D.,University of Mainz Medical Center | Schuppan D.,Beth Israel Deaconess Medical Center
Seminars in Liver Disease | Year: 2015

Abstract Significant progress has been made in understanding the principles underlying the development of liver fibrosis. This includes appreciating its dynamic nature, the importance of active fibrolysis in fibrosis regression, and the plasticity of cell populations endowing them with fibrogenic or fibrolytic properties. This is complemented by an increasing array of therapeutic targets with known roles in the progression or regression of fibrosis. With a key role for fibrosis in determining clinical outcomes and encouraging data from recently Food and Drug Administration-approved antifibrotics for pulmonary fibrosis, the development and validation of antifibrotic therapies has taken center stage in translational hepatology. In addition to summarizing the recent progress in antifibrotic therapies, the authors discuss some of the challenges ahead, such as achieving a better understanding of the interindividual heterogeneity of the fibrotic response, how to match interventions with the ideal patient population, and the development of better noninvasive methods to assess the dynamics of fibrogenesis and fibrolysis. Together, these advances will permit a better targeting and dose titration of individualized therapies. Finally, the authors discuss combination therapy with different antifibrotics as possibly the most potent approach for treating fibrosis in the liver. Copyright © 2015 by Thieme Medical. Source


Vaupel P.W.,TU Munich | Kelleher D.K.,University of Mainz Medical Center
International Journal of Hyperthermia | Year: 2010

Tumour blood flow before and during clinically relevant mild hyperthermia exhibits pronounced heterogeneity. Flow changes upon heating are not predictable and are both spatially and temporally highly variable. Flow increases may result in improved heat dissipation to the extent that therapeutically relevant tissue temperatures may not be achieved. This holds especially true for tumours or tumour regions in which flow rates are substantially higher than in the surrounding normal tissues. Changes in tumour oxygenation tend to reflect alterations in blood flow upon hyperthermia. An initial improvement in the oxygenation status, followed by a return to baseline levels (or even a drop to below baseline at high thermal doses) has been reported for some tumours, whereas a predictable and universal occurrence of sustained increases in O 2 tensions upon mild hyperthermia is questionable and still needs to be verified in the clinical setting. Clarification of the pathogenetic mechanisms behind possible sustained increases is mandatory. High-dose hyperthermia leads to a decrease in the extracellular and intracellular pH and a deterioration of the energy status, both of which are known to be parameters capable of acting as direct sensitisers and thus pivotal factors in hyperthermia treatment. The role of the tumour microcirculatory function, hypoxia, acidosis and energy status is complex and is further complicated by a pronounced heterogeneity. These latter aspects require additional critical evaluation in clinically relevant tumour models in order for their impact on the response to heat to be clarified. © 2010 Informa UK Ltd. Source


Diefenbach A.,University of Mainz Medical Center | Colonna M.,University of Washington | Koyasu S.,RIKEN | Koyasu S.,Keio University
Immunity | Year: 2014

Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILCs can be grouped into two separate lineages, cytotoxic ILCs represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILCs (i.e., ILC1s, ILC2s, ILC3s). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and Tcell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces. Innate lymphoid cells (ILCs) are important for protection against pathogens and for maintenance of organ homeostasis. Diefenbach and colleagues examine the core transcriptional circuitry required for commitment to the ILC lineage, as well as the transcriptional programs that drive differentiation into distinct ILC populations. © 2014 Elsevier Inc. Source

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