Stressful Presentations: Mild Cold Stress in Laboratory Mice Influences Phenotype of Dendritic Cells in Naïve and Tumor-Bearing Mice

Kokolus, Kathleen M.; Spangler, Haley; Povinelli, Benjamin; Farren, Matthew R.; Lee, Kelvin P.; Repasky, Elizabeth A.

doi:10.3389/fimmu.2014.00023

Cited by 54 publications

(63 citation statements)

References 104 publications

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“…The results suggest that activated DCs from tumor bearing mice at ST are less able to stimulate T cell proliferation than are DCs from tumor-bearing mice at TT [47]. Together, these studies from our group show that the balance of pro-tumorigenic cells (Tregs, MDSC) and antitumorigenic cells (CD8 + CTLs) is different at ST and TT, while antigen presentation may be suppressed at ST leading to reduced immune surveillance.…”

Section: Feeling Cold Tumor Immunology and Therapeutic Efficacy -Nomentioning

confidence: 67%

“…Comparisons of BAT by MRI could also prove to be a valuable and relevant biomarker of the degree of cold-stress in experimental mice at different ambient temperatures [40]. Sleep [79,94 ] Obesity [63,66,67 [7,10,12,[27][28][29]37,40,[42][43][44]46,47,63,66,67,70,71,79,84,89,93,94]). Several other conditions or phenomena that are modeled in mice and are likely to be influenced by housing temperature, but for which there is little or no published information are also listed (followed by ?).…”

Section: Resultsmentioning

confidence: 99%

“…In our experiments, we currently place cages within incubators (Thermo Fisher Scientific) maintained at 228 or 30 8C [42,44,47,48]. We have also used rooms with the temperature set at 228 or 30 8C, but working at 30 o C is indeed uncomfortable for the personnel.…”

Section: Metabol Ismmentioning

confidence: 99%

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Thermoneutrality, Mice, and Cancer: A Heated Opinion

Hylander

Repasky

2016

Trends in Cancer

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Section: Feeling Cold Tumor Immunology and Therapeutic Efficacy -Nomentioning

confidence: 67%

Section: Resultsmentioning

confidence: 99%

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Thermoneutrality, Mice, and Cancer: A Heated Opinion

Hylander

Repasky

2016

Trends in Cancer

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“…Although unlikely to be the only reason for the lack of translation from animal models to humans, temperature has recently been in the spotlight as an environmental factor that is extremely influential on mouse cancer models 36 . Mice housed at thermoneutrality (30 °C) are better able to fight tumor cells with improved adaptive immunity, resulting in reduced tumor growth relative to mice housed in typical temperatures (22 °C) 27,31,37 . Specifically, CD8 + T cell count and activation is improved in warmer temperatures 31 .…”

Section: Thermal Stress and Its Effect On Mouse Modelsmentioning

confidence: 99%

Stressed out: providing laboratory animals with behavioral control to reduce the physiological effects of stress

Gaskill

Garner

2017

Lab Anim

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Hans Selye would have made a horrible laboratory animal technician. This budding young 1930s scientist accidently discovered stress physiology and the negative effect chronic exposure has on the body because of his extremely poor rat handling skills 1 . As a result, we know for a fact that husbandry affects the quality of animal models. Despite this knowledge, most labs continue to ignore stressful experiences in rodent models, often because of time or financial costs. Today's researchers and animal technicians of course receive more training and animal welfare oversight than Dr. Selye, but the slow rate of progress in minimizing general stress in the laboratory is disheartening. In addition to the obvious animal welfare ramifications of this lack of advancement, animal models in general show poor predictive validity in terms of translational outcomes in human clinical trials. Roughly 90% of compounds (for example, drugs or other therapeutics) that are 'successful' in animal trials fail in FDA human trials; the majority of these failures are a result of a lack of efficacy 2 . There are certainly many variables that contribute to this failure to translate, including reliance on measures that lack biological or psychological homology, translation of human clinical measures, or simple environmental effects 3 . In addition, we widely assume that strain differences and genetics are a large, if not the largest, influence on mouse behavior. However, in a retrospective study of influences on thermal nociception, strain only accounted for 27% of data variability 4 . On the other hand, environmental factors alone accounted for as much as 42% of data variability in the same study, and the identity of the experimenter actually had more effect on behavior than the genetics of the animal. Other examples highlight even more marked ratios, with enormous effects on experimental power and false discovery rates if not properly accounted for in data analysis 3,5 . Yet there is a substantial lack of research and funding available to determine how the laboratory environment affects animal physiology and behavior, particularly as it relates to characteristics of the human disease being modeled.Temperature as an example of environmental stress Many aspects of the laboratory environment are stressful to rodents and do not accurately reflect human physiology. An animal's environment can include both physiological and social stressors that require an animal to adapt to maintain allostatic balance. Thermal stress, for example, is a known stressor in the laboratory that affects temperature regulation and metabolism and results in poor modeling of human conditions in mouse models. Laboratory mice experience some degree of thermal stress under all recommended housing temperatures 6,7 (typically between 20-26 °C), but are prevented from adequately using many of their behavioral adaptations for thermoregulation and must therefore rely on thermogenic processes. At 23 °C, a mouse's metabolic rate is 60% higher than its metabolic rate at thermoneu...

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“…The next four articles in this research topic are original research focusing on various aspects of DC function in vivo and in vitro (3)(4)(5)(6). DC maturation is induced by interaction with pathogenderived molecules such as LPS, but infections also induce production of a large number of cytokines.…”

mentioning

confidence: 99%

Dendritic Cell Control of Immune Responses

2016

Frontiers Research Topics

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Dendritic cells (DC) play a critical role in the initiation of the immune response, acting as sentinels in the tissues, reacting to invading pathogens and then inducing the activation and differentiation of naïve T cells. Since their discovery by Ralph Steinman in the 1970s, we have learned a great deal about DC biology and function. Distinct DC subsets exist in specific tissue niches and within the secondary lymph nodes, and the study of the phenotype and function of DC subsets in mice and humans has been an area of great interest. DC influence the immune response by directing the differentiation of T cells into functional subtypes important for elimination of the relevant pathogen. DC also contribute to disease pathogenesis, such as autoimmunity and cancer, through failures in self-tolerance and promotion of an immunosuppressive environment, respectively. In addition, because of their role in molding T cell responses, DC have been tested in therapeutic settings in both autoimmunity and cancer. In this research topic, 11 articles cover many aspects of current DC biology, ranging from the classification and function of DC subsets, roles of DC in disease pathogenesis to current use of DC in the therapeutic setting.The topic begins with two reviews of normal DC function; one is focused on the important topic of cross-presentation (1) and the other on human plasmacytoid (p)DC (2). Cross-presentation is the means by which DC are uniquely able to take up, process, and present exogenous antigens in MHC class I molecules and this review (1) describes novel findings on the role of intracellular vesicular traffic in this process and how it is influenced by inflammatory signals. pDCs were first identified as type 1 interferon-producing cells following acute viral infection and have also been shown to have tolerogenic properties. The review by Mathan et al. (2) focuses on interactions between human pDCs and other cells of the immune system with a particular emphasis on cell surface proteins that facilitate these interactions.The next four articles in this research topic are original research focusing on various aspects of DC function in vivo and in vitro (3-6). DC maturation is induced by interaction with pathogenderived molecules such as LPS, but infections also induce production of a large number of cytokines. Work by Hartmann et al. (3) examined the effects of virally induced cytokines on the maturation and function of human DC. These studies identified a set of five cytokines that are critical for the induction DC maturation. In addition, this study emphasizes a systems approach to studying the complex effects of cytokine-induced DC maturation (3). DC play an important role in maintaining tolerance to self-antigens and the second article in this section describes the role of early IL-10 production in induction of tolerance to a self-antigen (6). This article builds on the intriguing observation by the same group that immunization with foreign antigen induces a rapid upregulation of pancreatic enzymes in splenic DC th...

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Stressful Presentations: Mild Cold Stress in Laboratory Mice Influences Phenotype of Dendritic Cells in Naïve and Tumor-Bearing Mice

Cited by 54 publications

References 104 publications

Thermoneutrality, Mice, and Cancer: A Heated Opinion

Thermoneutrality, Mice, and Cancer: A Heated Opinion

Stressed out: providing laboratory animals with behavioral control to reduce the physiological effects of stress

Dendritic Cell Control of Immune Responses

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