Task Progress:
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We have provided major insights into the mechanisms underpinning the impaired NK-cell-mediated immunity observed during spaceflight. Specifically, we have shown that simulated microgravity impairs NK-cell function similarly to spaceflight and identified the specific cellular adaptations responsible, thus enabling the development of countermeasures to help maintain immunity during exploration class missions. Our findings have contributed to closing gaps Immune (IM) IM1, IM2, and IM8. For IM1, we have shown that spaceflight inhibits NK-cell function and we have shown that this inhibition can be recapitulated using simulated microgravity as an analog. We have also identified the specific cellular adaptations responsible for the microgravity-induced inhibition of NK-cells. For IM2, we have shown that an improved immunological standard is necessary for spaceflight. Specifically, NK-cell function should be monitored as impaired NK-cell function has been linked to increased cancer risk. Maintaining NK-cell function will be particularly important for long-duration space exploration when astronauts are being exposed to high levels of cosmic radiation for long periods of time. For IM8, our serum stimulation experiment will allow us to mechanistically link stress (through hormones and cytokines present in serum) during spaceflight to impaired NK-cell function.
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Articles in Peer-reviewed Journals
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Bigley AB, Rezvani K, Shah N, Sekine T, Balneger N, Pistillo M, Agha N, Kunz H, O'Connor DP, Bollard CM, Simpson RJ. "Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans." Clinical Experimental Immunology. 2016 Aug;185(2):239-51. https://doi.org/10.1111/cei.12785 ; PubMed PMID: 26940026; PubMed Central PMCID: PMC4955006 , Aug-2016
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Articles in Peer-reviewed Journals
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Bigley AB, Spielmann G, Agha N, O'Connor DP, Simpson RJ. "Dichotomous effects of latent CMV infection on the phenotype and functional properties of CD8+ T-cells and NK-cells." Cell Immunol. 2016 Feb;300:26-32. Epub 2015 Nov 24. https://doi.org/10.1016/j.cellimm.2015.11.005 ; PubMed PMID: 26651951 , Feb-2016
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Articles in Peer-reviewed Journals
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Simpson RJ, Bigley AB, Agha N, Hanley PJ, Bollard CM. "Mobilizing immune cells with exercise for cancer immunotherapy." Exerc Sport Sci Rev. 2017 Jul;45(3):163-72. https://doi.org/10.1249/JES.0000000000000114 ; PubMed PMID: 28418996 , Jul-2017
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Articles in Peer-reviewed Journals
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Gupta P, Bigley AB, Markofski M, Laughlin M, LaVoy EC. "Autologous serum collected 1h post-exercise enhances natural killer cell cytotoxicity." Brain Behav Immun. 2018 Jul;71:81-92. https://doi.org/10.1016/j.bbi.2018.04.007 ; PMID: 29656052 , Jul-2018
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Articles in Peer-reviewed Journals
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Bigley AB, Agha NH, Baker FL, Spielmann G, Kunz HE, Mylabathula PL, Rooney B, Laughlin MS, Pierson DL, Mehta SK, Crucian BE, Simpson RJ. "NK-cell function is impaired during long-duration spaceflight." J Appl Physiol (1985). 2019 Apr 1;126(4):842-53. Epub 2018 Nov 1. PubMed PMID: 30382809 ; https://doi.org/10.1152/japplphysiol.00761.2018 , Apr-2019
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Articles in Peer-reviewed Journals
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Mylabathula PL, Li L, Bigley AB, Markofski MM, Crucian BE, Mehta SK, Pierson DL, Laughlin MS, Rezvani K, Simpson RJ. "Simulated microgravity disarms human NK-cells and inhibits anti-tumor cytotoxicity in vitro." Acta Astronaut. 2020 Sep;174:32-40. https://doi.org/10.1016/j.actaastro.2020.03.023 , Sep-2020
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