Research article

Effects of spaceflight on the spleen and thymus of mice: Gene pathway analysis and immune infiltration analysis


  • Received: 10 December 2022 Revised: 31 January 2023 Accepted: 12 February 2023 Published: 03 March 2023
  • During space flight, the immune system function of the body is disrupted due to continuous weightlessness, radiation and other factors, resulting in an increased incidence of infectious diseases in astronauts. However, the effect of space flight on the immune system at the molecular level is unknown. The aim of this study was to identify key genes and pathways of spatial environmental effects on the spleen and thymus using bioinformatics analysis of the GEO dataset. Differentially expressed genes (DEGs) in the spleen and thymus of mice preflight and postflight were screened by comprehensive analysis of gene expression profile data. Then, GO enrichment analysis of DEGs was performed to determine the biological role of DEGs. A protein–protein interaction network was used to identify hub genes. In addition, transcription factors in DEGs were screened, and a TF-target regulatory network was constructed. Finally, immune infiltration analysis was performed on spleen and thymus samples from mice. The results showed that DEGs in the spleen and thymus are mainly involved in immune responses and in biological processes related to platelets. Six hub genes were identified in the spleen and 13 in the thymus, of which Ttr, Aldob, Gc and Fabp1 were common to both tissues. In addition, 5 transcription factors were present in the DEGs of the spleen, and 9 transcription factors were present in the DEGs of the thymus. The spatial environment can influence the degree of immune cell infiltration in the spleen and thymus. Our study bioinformatically analyzed the GEO dataset of spacefaring mice to identify the effects of the space environment on the immune system and the genes that play key roles, providing insights for the treatment of spaceflight-induced immune system disorders.

    Citation: Yuru Han, Shuo Shi, Shuang Liu, Xuefeng Gu. Effects of spaceflight on the spleen and thymus of mice: Gene pathway analysis and immune infiltration analysis[J]. Mathematical Biosciences and Engineering, 2023, 20(5): 8531-8545. doi: 10.3934/mbe.2023374

    Related Papers:

  • During space flight, the immune system function of the body is disrupted due to continuous weightlessness, radiation and other factors, resulting in an increased incidence of infectious diseases in astronauts. However, the effect of space flight on the immune system at the molecular level is unknown. The aim of this study was to identify key genes and pathways of spatial environmental effects on the spleen and thymus using bioinformatics analysis of the GEO dataset. Differentially expressed genes (DEGs) in the spleen and thymus of mice preflight and postflight were screened by comprehensive analysis of gene expression profile data. Then, GO enrichment analysis of DEGs was performed to determine the biological role of DEGs. A protein–protein interaction network was used to identify hub genes. In addition, transcription factors in DEGs were screened, and a TF-target regulatory network was constructed. Finally, immune infiltration analysis was performed on spleen and thymus samples from mice. The results showed that DEGs in the spleen and thymus are mainly involved in immune responses and in biological processes related to platelets. Six hub genes were identified in the spleen and 13 in the thymus, of which Ttr, Aldob, Gc and Fabp1 were common to both tissues. In addition, 5 transcription factors were present in the DEGs of the spleen, and 9 transcription factors were present in the DEGs of the thymus. The spatial environment can influence the degree of immune cell infiltration in the spleen and thymus. Our study bioinformatically analyzed the GEO dataset of spacefaring mice to identify the effects of the space environment on the immune system and the genes that play key roles, providing insights for the treatment of spaceflight-induced immune system disorders.



    加载中


    [1] J. J. Bong, Y. M. Kang, S. C. Shin, S. J. Choi, K. M. Lee, H. S. Kim, Identification of radiation-sensitive expressed genes in the ICR and AKR/J mouse thymus, Cell Biol. Int., 37 (2013), 485–494. https://doi.org/10.1002/cbin.10065 doi: 10.1002/cbin.10065
    [2] K. Horie, T. Kato, T. Kudo, H. Sasanuma, M. Miyauchi, N. Akiyama, et al., Impact of spaceflight on the murine thymus and mitigation by exposure to artificial gravity during spaceflight, Sci. Rep., 9 (2019), 19866. https://doi.org/10.1038/s41598-019-56432-9 doi: 10.1038/s41598-019-56432-9
    [3] R. Ito, L. P. Hale, S. M. Geyer, J. Li, A. Sornborger, J. Kajimura, et al., Late effects of exposure to ionizing radiation and age on human thymus morphology and function, Radiat. Res., 187 (2017), 589–598. https://doi.org/10.1667/rr4554.1 doi: 10.1667/rr4554.1
    [4] D. S. Gridley, X. W. Mao, L. S. Stodieck, V. L. Ferguson, T. A. Bateman, M. Moldovan, et al., Changes in mouse thymus and spleen after return from the STS-135 mission in space, PLoS One, 8 (2013), e75097. https://doi.org/10.1371/journal.pone.0075097 doi: 10.1371/journal.pone.0075097
    [5] E. C. Laiakis, I. Shuryak, A. Deziel, Y. W. Wang, B. L. Barnette, Y. Yu, et al., Effects of low dose space radiation exposures on the splenic metabolome, Int. J. Mol. Sci., 22 (2021). https://doi.org/10.3390/ijms22063070 doi: 10.3390/ijms22063070
    [6] E. G. Novoselova, S. M. Lunin, M. O. Khrenov, S. B. Parfenyuk, T. V. Novoselova, B. S. Shenkman, et al., Changes in immune cell signalling, apoptosis and stress response functions in mice returned from the BION-M1 mission in space, Immunobiology, 220 (2015), 500–509. https://doi.org/10.1016/j.imbio.2014.10.021 doi: 10.1016/j.imbio.2014.10.021
    [7] K. Horie, H. Sasanuma, T. Kudo, S. I. Fujita, M. Miyauchi, T. Miyao, et al., Down-regulation of GATA1-dependent erythrocyte-related genes in the spleens of mice exposed to a space travel, Sci. Rep., 9 (2019), 7654. https://doi.org/10.1038/s41598-019-44067-9 doi: 10.1038/s41598-019-44067-9
    [8] K. Felix, K. Wise, S. Manna, K. Yamauchi, B. L. Wilson, R. L. Thomas, et al., Altered cytokine expression in tissues of mice subjected to simulated microgravity, Mol. Cell. Biochem., 266 (2004), 79–85. https://doi.org/10.1023/b:mcbi.0000049136.55611.dd doi: 10.1023/b:mcbi.0000049136.55611.dd
    [9] T. Akiyama, K. Horie, E. Hinoi, M. Hiraiwa, A. Kato, Y. Maekawa, et al., How does spaceflight affect the acquired immune system, NPJ Microgravity, 6 (2020), 14. https://doi.org/10.1038/s41526-020-0104-1 doi: 10.1038/s41526-020-0104-1
    [10] C. C. Woods, K. E. Banks, R. Gruener, D. DeLuca, Loss of T cell precursors after spaceflight and exposure to vector-averaged gravity, Faseb J., 17 (2003), 1526–1528. https://doi.org/10.1096/fj.02-0749fje doi: 10.1096/fj.02-0749fje
    [11] R. Sadhukhan, D. Majumdar, S. Garg, R. D. Landes, V. McHargue, S. A. Pawar, et al., Simultaneous exposure to chronic irradiation and simulated microgravity differentially alters immune cell phenotype in mouse thymus and spleen, Life Sci. Space Res., 28 (2021), 66–73. https://doi.org/10.1016/j.lssr.2020.09.004 doi: 10.1016/j.lssr.2020.09.004
    [12] K. Chen, S. Liu, C. Lu, X. Gu, A prognostic and therapeutic hallmark developed by the integrated profile of basement membrane and immune infiltrative landscape in lung adenocarcinoma, Front. Immunol., 13 (2022), 1058493. https://doi.org/10.3389/fimmu.2022.1058493 doi: 10.3389/fimmu.2022.1058493
    [13] P. R. B. Dib, A. C. Quirino-Teixeira, L. B. Merij, M. B. M. Pinheiro, S. V. Rozini, F. B. Andrade, et al., Innate immune receptors in platelets and platelet-leukocyte interactions, J. Leukocyte Biol., 108 (2020), 1157–1182. https://doi.org/10.1002/jlb.4mr0620-701r doi: 10.1002/jlb.4mr0620-701r
    [14] D. Lai, L. Tan, X. Zuo, D. Liu, D. Jiao, G. Wan, et al., Prognostic ferroptosis-related lncRNA signatures associated with immunotherapy and chemotherapy responses in patients with stomach cancer, Front. Genet., 12 (2021), 798612. https://doi.org/10.3389/fgene.2021.798612 doi: 10.3389/fgene.2021.798612
    [15] K. Dai, Y. Wang, R. Yan, Q. Shi, Z. Wang, Y. Yuan, et al., Effects of microgravity and hypergravity on platelet functions, Thromb. Haemostasis, 101 (2009), 902–910. https://doi.org/10.1160/TH08-11-0750 doi: 10.1160/TH08-11-0750
    [16] K. Bednarska, B. Wachowicz, Changes in blood platelets exposed to UV-B radiation, J. Photochem. Photobiol. B Biol., 49 (1999), 187–191. https://doi.org/10.1016/s1011-1344(99)00057-3 doi: 10.1016/s1011-1344(99)00057-3
    [17] M. Shen, W. H. Frishman, Effects of spaceflight on cardiovascular physiology and health, Cardiol. Rev., 27 (2019), 122–126. https://doi.org/10.1097/crd.0000000000000236 doi: 10.1097/crd.0000000000000236
    [18] N. A. Vernice, C. Meydan, E. Afshinnekoo, C. E. Mason, Long-term spaceflight and the cardiovascular system, Precis. Clin. Med., 3 (2020), 284–291. https://doi.org/10.1093/pcmedi/pbaa022 doi: 10.1093/pcmedi/pbaa022
    [19] B. Lisowska-Myjak, A. Jóźwiak-Kisielewska, J. Łukaszkiewicz, E. Skarżyńska, Vitamin D-binding protein as a biomarker to confirm specific clinical diagnoses, Expert Rev. Mol. Diagn., 20 (2020), 49–56. https://doi.org/10.1080/14737159.2020.1699064 doi: 10.1080/14737159.2020.1699064
    [20] S. Liu, C. Ni, Y. Li, H. Yin, C. Xing, Y. Yuan, et al., The involvement of TRIB3 and FABP1 and their potential functions in the dynamic process of gastric cancer, Front. Mol. Biosci., 8 (2021), 790433. https://doi.org/10.3389/fmolb.2021.790433 doi: 10.3389/fmolb.2021.790433
    [21] N. Vuilleumier, J. M. Dayer, A. von Eckardstein, P. Roux-Lombard, Pro- or anti-inflammatory role of apolipoprotein A-1 in high-density lipoproteins, Swiss Med. Wkly, 143 (2013), w13781. https://doi.org/10.4414/smw.2013.13781 doi: 10.4414/smw.2013.13781
    [22] M. Blank, Y. Shoenfeld, Histidine-rich glycoprotein modulation of immune/autoimmune, vascular, and coagulation systems, Clin. Rev. Allergy Immunol., 34 (2008), 307–312. https://doi.org/10.1007/s12016-007-8058-6 doi: 10.1007/s12016-007-8058-6
    [23] H. Wang, D. Liu, P. Song, F. Jiang, X. Chi, T. Zhang, Exposure to hypoxia causes stress erythropoiesis and downregulates immune response genes in spleen of mice, BMC Genomics, 22 (2021), 413. https://doi.org/10.1186/s12864-021-07731-x doi: 10.1186/s12864-021-07731-x
    [24] B. Dumitriu, M. R. Patrick, J. P. Petschek, S. Cherukuri, U. Klingmuller, P. L. Fox, et al., Sox6 cell-autonomously stimulates erythroid cell survival, proliferation, and terminal maturation and is thereby an important enhancer of definitive erythropoiesis during mouse development, Blood, 108 (2006), 1198–1207. https://doi.org/10.1182/blood-2006-02-004184 doi: 10.1182/blood-2006-02-004184
    [25] E. Ozçivici, Effects of spaceflight on cells of bone marrow origin, Turk. J. Hematol., 30 (2013), 1–7. https://doi.org/10.4274/tjh.2012.0127 doi: 10.4274/tjh.2012.0127
    [26] T. Elsir, A. Smits, M. S. Lindström, M. Nistér, Transcription factor PROX1: its role in development and cancer, Cancer Metastasis Rev., 31 (2012), 793–805. https://doi.org/10.1007/s10555-012-9390-8 doi: 10.1007/s10555-012-9390-8
    [27] W. H. Liu, M. Z. Lai, Deltex regulates T-cell activation by targeted degradation of active MEKK1, Mol. Cell. Biol., 25 (2005), 1367–1378. https://doi.org/10.1128/mcb.25.4.1367-1378.2005 doi: 10.1128/mcb.25.4.1367-1378.2005
    [28] P. Yu, J. K. Tung, M. Simons, Lymphatic fate specification: an ERK-controlled transcriptional program, Microvasc. Res., 96 (2014), 10–15. https://doi.org/10.1016/j.mvr.2014.07.016 doi: 10.1016/j.mvr.2014.07.016
    [29] M. Middelhoff, H. Nienhüser, G. Valenti, H. C. Maurer, Y. Hayakawa, R. Takahashi, et al., Prox1-positive cells monitor and sustain the murine intestinal epithelial cholinergic niche, Nat. Commun., 11 (2020), 111. https://doi.org/10.1038/s41467-019-13850-7 doi: 10.1038/s41467-019-13850-7
    [30] J. E. Park, R. A. Botting, C. Conde, D. M. Popescu, M. Lavaert, D. J. Kunz, et al., A cell atlas of human thymic development defines T cell repertoire formation, Science, 367 (2020). https://doi.org/10.1126/science.aay3224 doi: 10.1126/science.aay3224
    [31] M. Y. Matsumoto, H. Matsuo, T. Oka, T. Fukudome, K. Hayashi, H. Shiraishi, et al., Thymic myoid cells as a myasthenogenic antigen and antigen-presenting cells, J. Neuroimmunol., 150 (2004), 80–87. https://doi.org/10.1016/j.jneuroim.2004.01.022 doi: 10.1016/j.jneuroim.2004.01.022
    [32] M. Rajabinejad, S. Ranjbar, L. Afshar Hezarkhani, F. Salari, A. Gorgin Karaji, A. Rezaiemanesh, Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review, J. Cell. Physiol., 235 (2020), 5030–5040. https://doi.org/10.1002/jcp.29401 doi: 10.1002/jcp.29401
    [33] A. Avdeeva, Y. Rubtsov, D. Dyikanov, T. Popkova, E. Nasonov, Regulatory T cells in patients with early untreated rheumatoid arthritis: Phenotypic changes in the course of methotrexate treatment, Biochimie, 174 (2020), 9–17. https://doi.org/10.1016/j.biochi.2020.03.014 doi: 10.1016/j.biochi.2020.03.014
    [34] A. O. Naufel, M. C. F. Aguiar, F. M. Madeira, L. G. Abreu, Treg and Th17 cells in inflammatory periapical disease: a systematic review, Braz. Oral. Res., 31 (2017). https://doi.org/10.1590/1807-3107bor-2017.vol31.0103 doi: 10.1590/1807-3107bor-2017.vol31.0103
    [35] J. B. Yan, M. M. Luo, Z. Y. Chen, B. H. He, The function and role of the Th17/Treg cell balance in inflammatory bowel disease, J. Immunol. Res., 2020 (2020), 8813558. https://doi.org/10.1155/2020/8813558 doi: 10.1155/2020/8813558
  • Reader Comments
  • © 2023 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(2026) PDF downloads(133) Cited by(0)

Article outline

Figures and Tables

Figures(7)  /  Tables(1)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog