Exercise-induced Natural Killer Cell Activation is Driven by Epigenetic Modifications

Zimmer, Philipp; Bloch, Wilhelm; Schenk, Alexander; Zopf, Eva M.; Hildebrandt, Ursula; Streckmann, Fiona; Beulertz, Julia; Koliamitra, Christine; Schollmayer, Friederike; Baumann, Freerk T.

doi:10.1055/s-0034-1398531

Cited by 55 publications

(30 citation statements)

References 25 publications

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“…Both authors independently reviewed the full-text articles and determined that 36 studies were not eligible for review for the following reasons: study was not published in English (n=1), no full-text was available (n=12), no control group (n=3), no PA intervention (n=6), multiple program features (n=1), protocol article (n=2), no health and/or QOL outcome reported (n=1), and age criteria not met (n=10). For those studies that were excluded because of the age criteria, participants were either above the defined age range [48-55] or samples were comprised of ≤50% adolescents [56,57]. This left 2 articles that met the predetermined eligibility criteria [58,59].…”

Section: Resultsmentioning

confidence: 99%

The Effects of Physical Activity on Health and Quality of Life in Adolescent Cancer Survivors: A Systematic Review

Wurz¹,

Brunet²

2016

JMIR Cancer

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BackgroundThere are numerous published controlled trials assessing the safety and the benefits of physical activity (PA) for child and adult cancer survivors. However, trials exclusively comprised of adolescent cancer survivors aged 13-19 years, who may experience different health and quality of life (QOL) effects as a function of their developmental status, are lacking. Rather, some trials have included both adolescent and child cancer survivors together.ObjectiveThe aim of this systematic review was to synthesize the findings from randomized controlled trails (RCTs) and controlled clinical trials (CCTs) investigating the effects of PA on health and QOL outcomes in samples comprised of >50% adolescent cancer survivors to summarize the current state of evidence, identify knowledge gaps, and highlight areas in need of additional research within this population.MethodsUsing a search strategy developed for this review, 10 electronic databases were searched for RCTs and CCTs that reported on the effects of PA on at least 1 health and/or QOL outcome in samples comprised of >50% adolescent cancer survivors.ResultsFrom the 2249 articles identified, 2 CCTs met the predetermined eligibility criteria and were included in this review. Combined, 28 adolescents (of 41 participants) who were receiving active treatment participated in the 2 studies reviewed. A total of 4 health and QOL outcomes (ie, bone mass, fatigue, grip strength, QOL) were assessed pre- and post-PA intervention.ConclusionsOn the basis of the 2 studies reviewed, PA appears to be safe and feasible. PA also shows promise to mitigate reductions in bone mass and might be a viable strategy to improve fatigue, grip strength, and QOL. High-quality controlled trials with larger samples exclusively comprised of adolescent cancer survivors that assess a wide range of outcomes are needed to determine the effects of PA on health and QOL outcomes in this population.

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Section: Resultsmentioning

confidence: 99%

The Effects of Physical Activity on Health and Quality of Life in Adolescent Cancer Survivors: A Systematic Review

Wurz¹,

Brunet²

2016

JMIR Cancer

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“…Whereas, two studies demonstrated an increase in the CD56 dim CD16 bright NK cell subset, other studies demonstrated a higher frequency of the CD56 bright CD16 dim/neg NK cell subpopulation (86,203,209,210). However, physical activity increased the expression of the activating NK cell receptors CD69 and NKG2D and the degranulation marker CD107a as well as the IFN-γ, perforin, and granzyme B content of NK cells (73,196,203,211). Furthermore, the expression of the inhibitory NK cell receptor KLRG1 was reduced after exercise training (203).…”

Section: Reactivation Of Nk Cells By Body Weight Reduction and Physicmentioning

confidence: 97%

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

et al. 2020

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Obesity is accompanied by a systemic chronic low-grade inflammation as well as dysfunctions of several innate and adaptive immune cells. Recent findings emphasize an impaired functionality and phenotype of natural killer (NK) cells under obese conditions. This review provides a detailed overview on research related to overweight and obesity with a particular focus on NK cells. We discuss obesity-associated alterations in subsets, distribution, phenotype, cytotoxicity, cytokine secretion, and signaling cascades of NK cells investigated in vitro as well as in animal and human studies. In addition, we provide recent insights into the effects of physical activity and obesity-associated nutritional factors as well as the reduction of body weight and fat mass on NK cell functions of obese individuals. Finally, we highlight the impact of impaired NK cell physiology on obesity-associated diseases, focusing on the elevated susceptibility for viral infections and increased risk for cancer development and impaired treatment response.NK cells are large granular lymphocytes that mediate rapid innate immunity against viruses, bacteria, parasites, and tumor cells without prior sensitization. NK cells primarily develop and mature in the bone marrow, migrate through the bloodstream, and seed into secondary lymphoid organs, like thymus, spleen, and lymph nodes as well as in other peripheral tissues, like lung, liver, kidney, uterus, and the gastrointestinal tract (23). In blood, NK cells represent 1-6% of all leukocytes and comprise up to 15% of human peripheral blood mononuclear cells (PBMCs). Human NK cells have been defined by the expression of adhesion molecule CD56 and by the absence of the T cell marker CD3. Based on their expression level of CD56 and the Fcγ receptor CD16, NK cells are subdivided into different subpopulations. The two major and classically defined subsets are the CD56 dim CD16 bright NK cells and the CD56 bright CD16 dim/neg NK cells. CD56 dim CD16 bright NK cells represent about 90% of all NK cells and are predominantly found in peripheral blood (24). They are mostly responsible for cytotoxic activity and target cell killing but are also a source of pro-inflammatory Abbreviations: ACM, adipocyte-conditioned media; Adamts3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 3; AdipoR, adiponectin receptor; Anxa8, annexin A8; AT, adipose tissue; Bax, Bcl-2-associated X protein; Bcl, B-cell lymphoma; BMI, body mass index; CCR, CC chemokine receptor; Csf1r, colony stimulating factor 1 receptor; CX3CR1, C-X3-C-motif chemokine receptor 1; DNAM-1, DNAX accessory molecule-1; ESR, estrogen receptor; FasL, Fas ligand; IFN-γ, interferon; GM-CSF; granulocyte macrophage colony-stimulating factor; H6pd, hexose-6-phosphate dehydrogenase; Hk2, hexokinase 2; IL, interleukinIL-6R; interleukin-6 receptor; Il18rap, interleukin 18 receptor accessory protein; IP-10, interferon gamma-induced protein 10; JAK, Janus kinase; KIR, killer immunoglobulin-like receptor; Klra1, killer lectin-like receptor subfamil...

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“…Recently, Zimmer et al. (, ) found increases in histone acetylation and DNA methylation with endurance exercise, and found an up‐regulation of gene transcription for NK cell activation receptors. Acute exercise bouts can increase the expression of the killer‐cell immunoglobulin‐like receptor (KIR) gene (Maltseva et al.…”

Section: Discussionmentioning

confidence: 99%

Intermittent and graded exercise effects on NK cell degranulation markers LAMP‐1/LAMP‐2 and CD8⁺CD38⁺ in chronic fatigue syndrome/myalgic encephalomyelitis

Broadbent

Coutts

2017

Physiological Reports

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There is substantial evidence of immune system dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) but little is understood of exercise training effects on lymphocyte function in this illness. This study investigated whether graded and intermittent exercise improved CD8+ lymphocyte activation and natural killer cell degranulation markers compared to no exercise. Twenty‐four chronic fatigue syndrome (CFS) patients (50.2 ± 10 year) were randomized to graded exercise (GE), intermittent exercise (IE) or usual care (UC) groups; a control group (CTL) of 18 matched sedentary non‐CFS/ME participants were included for immunological variable comparisons. Main outcome measures were pre‐ and postintervention expression of CD3+ CD8+ CD38+ and CD3− CD16+56+ CD107a+ (LAMP‐1) CD107b+ (LAMP‐2) and aerobic exercise capacity. The postintervention percentage of NK cells expressing LAMP‐1 and ‐2 was significantly higher in IE compared to UC, and higher in GE compared to UC and CTL. LAMP‐1 and LAMP‐2 expression (absolute numbers and percent positive) increased significantly pre‐to‐postintervention for both GE and IE. Preintervention, the absolute number of CD8+ CD38+ cells was significantly lower in CTL compared to UC and IE. There were no significant pre‐ to postintervention changes in CD8+ CD38+ expression for any group. Aerobic exercise capacity was significantly improved by GE and IE. Twelve weeks of GE and IE increased the expression of NK cell activation and degranulation markers, suggesting enhanced immunosurveillance. Low‐intensity exercise may also reduce CD8+ CD38+ expression, a marker of inflammation. Both GE and IE improved exercise capacity without worsening CFS/ME symptoms, and more robust trials of these exercise modalities are warranted.

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Exercise-induced Natural Killer Cell Activation is Driven by Epigenetic Modifications

Cited by 55 publications

References 25 publications

The Effects of Physical Activity on Health and Quality of Life in Adolescent Cancer Survivors: A Systematic Review

The Effects of Physical Activity on Health and Quality of Life in Adolescent Cancer Survivors: A Systematic Review

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

Intermittent and graded exercise effects on NK cell degranulation markers LAMP‐1/LAMP‐2 and CD8⁺CD38⁺ in chronic fatigue syndrome/myalgic encephalomyelitis

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Exercise-induced Natural Killer Cell Activation is Driven by Epigenetic Modifications

Cited by 55 publications

References 25 publications

The Effects of Physical Activity on Health and Quality of Life in Adolescent Cancer Survivors: A Systematic Review

The Effects of Physical Activity on Health and Quality of Life in Adolescent Cancer Survivors: A Systematic Review

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

Intermittent and graded exercise effects on NK cell degranulation markers LAMP‐1/LAMP‐2 and CD8+CD38+ in chronic fatigue syndrome/myalgic encephalomyelitis

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Product

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Intermittent and graded exercise effects on NK cell degranulation markers LAMP‐1/LAMP‐2 and CD8⁺CD38⁺ in chronic fatigue syndrome/myalgic encephalomyelitis