Skip to main content

Advertisement

SpringerLink
Log in

Vitamins A and D Enhance the Expression of Ror-γ-Targeting miRNAs in a Mouse Model of Multiple Sclerosis

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Autoreactive T cells, particularly those characterized by a Th17 phenotype, exert significant influence on the pathogenesis of multiple sclerosis (MS). The present study aimed to elucidate the impact of individual and combined administration of vitamin A and D on neuroinflammation, and microRNAs (miRNAs) involved in T helper (Th)17 development, utilizing a murine model of experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice, and 3 days prior to immunization, intraperitoneal injections of vitamins A and D or their combination were administered. Th17 cell percentages were determined in splenocytes utilizing intracellular staining and flow cytometry. Furthermore, the expression of Ror γ-t, miR-98-5p and Let-7a-5p, was measured in both splenocytes and spinal cord tissues using RT-PCR. Treatment with vitamin A and D resulted in a reduction in both disease severity in EAE mice. Treated mice showed a decreased frequency of Th17 cells and lower expression levels of IL17 and Ror γ-t in splenocytes and spinal cord. The spinal cord tissues and splenocytes of mice treated with vitamins A, D, and combined A+D showed a significant upregulation of miR-98-5p and Let-7a-5p compared to the EAE group. Statistical analysis indicated a strong negative correlation between miR-98-5p and Let-7a-5p levels in splenocytes and Ror-t expression. Our findings indicate that the administration of vitamins A and D exerts a suppressive effect on neuroinflammation in EAE that is associated with a reduction in the differentiation of T cells into the Th17 phenotype and is mediated by the upregulation of miR-98-5p and Let-7a-5p, which target the Ror γ-t.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Sospedra M, Martin R (2016) Immunology of multiple sclerosis: Seminars in neurology. Thieme Medical Publishers, pp. 115–127

    Google Scholar 

  2. Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15:545–558

    Article  CAS  PubMed  Google Scholar 

  3. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S (2015) Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurol 28:206–219

    Article  CAS  PubMed  Google Scholar 

  4. Moser T, Akgun K, Proschmann U, Sellner J, Ziemssen T (2020) The role of TH17 cells in multiple sclerosis: therapeutic implications. Autoimmun Rev 19:102647

    Article  CAS  PubMed  Google Scholar 

  5. Balasa R, Barcutean L, Balasa A, Motataianu A, Roman-Filip C, Manu D (2020) The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum Immunol 81:237–243

    Article  CAS  PubMed  Google Scholar 

  6. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N et al (2007) Human TH 17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13:1173–1175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Larochelle C, Wasser B, Jamann H, Loffel JT, Cui QL, Tastet O, Schillner M, Luchtman D et al (2021) Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation. Proc Natl Acad Sci U S A 118:e2025813118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu M, Hu X, Wang Y, Peng F, Yang Y, Chen X, Lu Z, Zheng X (2009) Effect of high-dose methylprednisolone treatment on Th17 cells in patients with multiple sclerosis in relapse. Acta Neurol Scand 120:235–241

    Article  CAS  PubMed  Google Scholar 

  9. Ramgolam VS, Markovic-Plese S (2010) Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets 10:161–167

    Article  CAS  PubMed  Google Scholar 

  10. Mehling M, Lindberg R, Raulf F, Kuhle J, Hess C, Kappos L, Brinkmann V (2010) Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology 75:403–410

    Article  CAS  PubMed  Google Scholar 

  11. Sweeney CM, Lonergan R, Basdeo SA, Kinsella K, Dungan LS, Higgins SC, Kelly PJ, Costelloe L et al (2011) IL-27 mediates the response to IFN-beta therapy in multiple sclerosis patients by inhibiting Th17 cells. Brain Behav Immun 25:1170–1181

    Article  CAS  PubMed  Google Scholar 

  12. Darlington PJ, Touil T, Doucet JS, Gaucher D, Zeidan J, Gauchat D, Corsini R, Kim HJ et al (2013) Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Ann Neurol 73:341–354

    Article  CAS  PubMed  Google Scholar 

  13. Sato DK, Nakashima I, Bar-Or A, Misu T, Suzuki C, Nishiyama S, Kuroda H, Fujihara K et al (2014) Changes in Th17 and regulatory T cells after fingolimod initiation to treat multiple sclerosis. J Neuroimmunol 268:95–98

    Article  CAS  PubMed  Google Scholar 

  14. Hosseini A, Gharibi T, Mohammadzadeh A, Ebrahimi-Kalan A, Jadidi-Niaragh F, Babaloo Z, Shanehbandi D, Baghbani E et al (2021) Ruxolitinib attenuates experimental autoimmune encephalomyelitis (EAE) development as animal models of multiple sclerosis (MS). Life Sci 276:119395

    Article  CAS  PubMed  Google Scholar 

  15. Jafarzadeh A, Azizi SV, Arabi Z, Ahangar-Parvin R, Mohammadi-Kordkhayli M, Larussa T, Khatami F, Nemati M (2019) Vitamin D down-regulates the expression of some Th17 cell-related cytokines, key inflammatory chemokines, and chemokine receptors in experimental autoimmune encephalomyelitis. Nutr Neurosci 22:725–737

    Article  CAS  PubMed  Google Scholar 

  16. Zhang J, Cheng Y, Cui W, Li M, Li B, Guo L (2014) MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol 266:56–63

    Article  CAS  PubMed  Google Scholar 

  17. Riccio P, Rossano R (2015) Nutrition facts in multiple sclerosis. ASN Neuro 7:1759091414568185

    Article  PubMed  PubMed Central  Google Scholar 

  18. Evans E, Levasseur V, Cross AH, Piccio L (2019) An overview of the current state of evidence for the role of specific diets in multiple sclerosis. Mult Scler Relat Disord 36:101393

    Article  PubMed  Google Scholar 

  19. von Geldern G, Mowry EM (2012) The influence of nutritional factors on the prognosis of multiple sclerosis. Nat Rev Neurol 8:678–689

    Article  Google Scholar 

  20. Yeh WZ, Gresle M, Jokubaitis V, Stankovich J, van der Walt A, Butzkueven H (2020) Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis. Br J Pharmacol 177:4113–4133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sintzel MB, Rametta M, Reder AT (2018) Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther 7:59–85

    Article  PubMed  Google Scholar 

  22. Fragoso YD, Stoney PN, McCaffery PJ (2014) The evidence for a beneficial role of vitamin A in multiple sclerosis. CNS Drugs 28:291–299

    Article  CAS  PubMed  Google Scholar 

  23. Evans E, Piccio L, Cross AH (2018) Use of vitamins and dietary supplements by patients with multiple sclerosis: a review. JAMA Neurol 75:1013–1021

    Article  PubMed  Google Scholar 

  24. Mohammadi-Kordkhayli M, Ahangar-Parvin R, Azizi SV, Nemati M, Shamsizadeh A, Khaksari M, Moazzeni SM, Jafarzadeh A (2015) Vitamin D modulates the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis. Iran J Immunol 12:35–49

    PubMed  Google Scholar 

  25. Jafarzadeh A, Ahangar-Parvin R, Azizi S, Ayobi F, Taghipour Z, Shamsizadeh A (2015) Evaluation of the effect of vitamin D3 and ginger extract on the clinical symptoms and the severity of inflammation in EAE. JRUMS 13:683–694

    Google Scholar 

  26. Abdolahi M, Yavari P, Honarvar NM, Bitarafan S, Mahmoudi M, Saboor-Yaraghi AA (2015) Molecular mechanisms of the action of vitamin A in Th17/Treg axis in multiple sclerosis. J Mol Neurosci 57:605–613

    Article  CAS  PubMed  Google Scholar 

  27. Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, O'Shea JJ (2008) Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 111:1013–1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Parastouei K, Solaymani-Mohammadi F, Shiri-Shahsavar MR, Chahardoli R, Nasl-Khameneh AM, Zarandi MB, Ghotloo S, Saboor-Yaraghi AA (2020) The effect of calcitriol and all-trans retinoic acid on T-bet, IFN-γ, GATA3 and IL-4 genes expression in experimental autoimmune encephalomyelitis. Apmis 128:583–592

    Article  CAS  PubMed  Google Scholar 

  29. Kordkhayli MM, Mansouri F, Talebi F, Noorbakhsh F, Saboor-Yaraghi AA (2022) Influence of vitamins A and D on the expression of MicroRNA27-3p isoforms and GATA3 in experimental autoimmune encephalomyelitis. Iran J Allergy Asthma Immunol 21:429–440

    Google Scholar 

  30. Oksenberg JR, Baranzini SE, Sawcer S, Hauser SL (2008) The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat Rev Genet 9:516–526

    Article  CAS  PubMed  Google Scholar 

  31. Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV (2010) Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol 6:156–166

    Article  PubMed  Google Scholar 

  32. Junker A, Hohlfeld R, Meinl E (2011) The emerging role of microRNAs in multiple sclerosis. Nat Rev Neurol 7:56–59

    Article  CAS  PubMed  Google Scholar 

  33. Koch MW, Metz LM, Kovalchuk O (2013) Epigenetic changes in patients with multiple sclerosis. Nat Rev Neurol 9:35–43

    Article  CAS  PubMed  Google Scholar 

  34. Lu TX, Rothenberg ME (2018) MicroRNA. J Allergy Clin Immunol 141:1202–1207

    Article  CAS  PubMed  Google Scholar 

  35. O'Connell RM, Rao DS, Chaudhuri AA, Baltimore D (2010) Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 10:111–122

    Article  CAS  PubMed  Google Scholar 

  36. Mehta A, Baltimore D (2016) MicroRNAs as regulatory elements in immune system logic. Nat Rev Immunol 16:279–294

    Article  CAS  PubMed  Google Scholar 

  37. Bushati N, Cohen SM (2007) microRNA functions. Annu Rev Cell Dev Biol 23:175–205

    Article  CAS  PubMed  Google Scholar 

  38. Liu C, Yang H, Shi W, Wang T, Ruan Q (2018) MicroRNA-mediated regulation of T helper type 17/regulatory T-cell balance in autoimmune disease. Immunology 155:427–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jeker LT, Bluestone JA (2013) MicroRNA regulation of T-cell differentiation and function. Immunol Rev 253:65–81

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kunze-Schumacher H, Krueger A (2020) The role of microRNAs in development and function of regulatory T cells - lessons for a better understanding of microRNA biology. Front Immunol 11:2185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Maul J, Alterauge D, Baumjohann D (2019) MicroRNA-mediated regulation of T follicular helper and T follicular regulatory cell identity. Immunol Rev 288:97–111

    Article  CAS  PubMed  Google Scholar 

  42. Simpson LJ, Ansel KM (2015) MicroRNA regulation of lymphocyte tolerance and autoimmunity. J Clin Invest 125:2242–2249

    Article  PubMed  PubMed Central  Google Scholar 

  43. Saito Y, Saito H, Liang G, Friedman JM (2014) Epigenetic alterations and microRNA misexpression in cancer and autoimmune diseases: a critical review. Clin Rev Allergy Immunol 47:128–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhu S, Pan W, Qian Y (2013) MicroRNA in immunity and autoimmunity. J Mol Med (Berl) 91:1039–1050

    Article  CAS  PubMed  Google Scholar 

  45. Chen C, Zhou Y, Wang J, Yan Y, Peng L, Qiu W (2018) Dysregulated microRNA involvement in multiple sclerosis by induction of T helper 17 cell differentiation. Front Immunol 9:1256

    Article  PubMed  PubMed Central  Google Scholar 

  46. Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z et al (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10:1252–1259

    Article  CAS  PubMed  Google Scholar 

  47. Ghorbani S, Talebi F, Chan WF, Masoumi F, Vojgani M, Power C, Noorbakhsh F (2017) MicroRNA-181 variants regulate T cell phenotype in the context of autoimmune neuroinflammation. Front Immunol 8:758

    Article  PubMed  PubMed Central  Google Scholar 

  48. Rezaei N, Talebi F, Ghorbani S, Rezaei A, Esmaeili A, Noorbakhsh F, Hakemi MG (2019) MicroRNA-92a drives Th1 responses in the experimental autoimmune encephalomyelitis. Inflammation 42:235–245

    Article  CAS  PubMed  Google Scholar 

  49. Talebi F, Ghorbani S, Chan WF, Boghozian R, Masoumi F, Ghasemi S, Vojgani M, Power C et al (2017) MicroRNA-142 regulates inflammation and T cell differentiation in an animal model of multiple sclerosis. J Neuroinflammation 14:55

    Article  PubMed  PubMed Central  Google Scholar 

  50. Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, Lassmann H, Wekerle H et al (2009) MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 132:3342–3352

    Article  PubMed  Google Scholar 

  51. Gholikhani-Darbroud R (2020) MicroRNA and retinoic acid. Clinica Chimica Acta 502:15–24

    Article  CAS  Google Scholar 

  52. Takahashi H, Kanno T, Nakayamada S, Hirahara K, Sciumè G, Muljo SA, Kuchen S, Casellas R et al (2012) TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol 13:587–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li YC, Chen Y, Liu W, Thadhani R (2014) MicroRNA-mediated mechanism of vitamin D regulation of innate immune response. J Steroid Biochem Mol Biol 144:81–86

    Article  CAS  PubMed  Google Scholar 

  54. Giuliani F, Metz LM, Wilson T, Fan Y, Bar-Or A, Yong VW (2005) Additive effect of the combination of glatiramer acetate and minocycline in a model of MS. J Neuroimmunol 158:213–221

    Article  CAS  PubMed  Google Scholar 

  55. Parastouei K, Mirshafiey A, Eshraghian MR, Shiri-Shahsavar MR, Solaymani-Mohammadi F, Chahardoli R, Alvandi E, Saboor-Yaraghi AA (2018) The effect of 1, 25 (OH) 2 D3 (calcitriol) alone and in combination with all-trans retinoic acid on ROR-γt, IL-17, TGF-β, and FOXP3 gene expression in experimental autoimmune encephalomyelitis. Nutr Neurosci 21:210–218

    Article  CAS  PubMed  Google Scholar 

  56. Joshi S, Pantalena L-C, Liu XK, Gaffen SL, Liu H, Rohowsky-Kochan C, Ichiyama K, Yoshimura A et al (2011) 1, 25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 31:3653–3669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Keino H, Watanabe T, Sato Y, Okada AA (2010) Anti-inflammatory effect of retinoic acid on experimental autoimmune uveoretinitis. Br J Ophthalmol 94:802–807

    Article  PubMed  Google Scholar 

  58. Griffin MD, Xing N, Kumar R (2003) Vitamin D and its analogs as regulators of immune activation and antigen presentation. Annu Rev Nutr 23:117–145

    Article  CAS  PubMed  Google Scholar 

  59. Mora JR, Iwata M, von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8:685–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Raverdeau M, Christofi M, Malara A, Wilk MM, Misiak A, Kuffova L, Yu T, McGinley AM et al (2019) Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity. EMBO Rep 20:e47121

    Article  PubMed  PubMed Central  Google Scholar 

  61. Zhan XX, Liu Y, Yang JF, Wang GY, Mu L, Zhang TS, Xie XL, Wang JH et al (2013) All-trans-retinoic acid ameliorates experimental allergic encephalomyelitis by affecting dendritic cell and monocyte development. Immunology 138:333–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mimura LAN, Fraga-Silva TFC, Oliveira LRC, Ishikawa LLW, Borim PA, Machado CM, Junior J, Fonseca DMD, Sartori A (2021) Preclinical therapy with vitamin D3 in experimental encephalomyelitis: efficacy and comparison with paricalcitol. Int J Mol Sci 22:1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Spanier JA, Nashold FE, Nelson CD, Praska CE, Hayes CE (2020) Vitamin D3-mediated resistance to a multiple sclerosis model disease depends on myeloid cell 1,25-dihydroxyvitamin D3 synthesis and correlates with increased CD4(+) T cell CTLA-4 expression. J Neuroimmunol 338:577105

    Article  CAS  PubMed  Google Scholar 

  64. Cao Q, Zheng C, Xie Z, Liu L, Zhu J, Jin T (2020) The change of PD1, PDL1 in experimental autoimmune encephalomyelitis treated by 1,25(OH)2D3. J Neuroimmunol 338:577079

    Article  CAS  PubMed  Google Scholar 

  65. Moore JR, Hubler SL, Nelson CD, Nashold FE, Spanier JA, Hayes CE (2018) 1,25-Dihydroxyvitamin D3 increases the methionine cycle, CD4(+) T cell DNA methylation and Helios(+)Foxp3(+) T regulatory cells to reverse autoimmune neurodegenerative disease. J Neuroimmunol 324:100–114

    Article  CAS  PubMed  Google Scholar 

  66. Lindsay MA (2008) MicroRNAs and the immune response. Trends Immunol 29:343–351

    Article  CAS  PubMed  Google Scholar 

  67. Brodersen P, Voinnet O (2009) Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 10:141–148

    Article  CAS  PubMed  Google Scholar 

  68. Noorbakhsh F, Ellestad KK, Maingat F, Warren KG, Han MH, Steinman L, Baker GB, Power C (2011) Impaired neurosteroid synthesis in multiple sclerosis. Brain 134:2703–2721

    Article  PubMed  PubMed Central  Google Scholar 

  69. Parker MI, Palladino MA (2017) MicroRNAs downregulated following immune activation of rat testis. Am J Reprod Immunol 00:e12673. https://doi.org/10.1111/aji.12673

  70. Peng Y, Wang Q, Yang W, Yang Q, Pei Y, Zhang W (2020) MiR-98-5p expression inhibits polarization of macrophages to an M2 phenotype by targeting Trib1 in inflammatory bowel disease. Acta Biochim Pol 67:157–163

    CAS  PubMed  Google Scholar 

  71. Zhang J, Han L, Chen F (2021) Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps. Diagn Pathol 16:27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Stockinger B, Veldhoen M (2007) Differentiation and function of Th17 T cells. Curr Opin Immunol 19:281–286

    Article  CAS  PubMed  Google Scholar 

  73. Luckheeram RV, Zhou R, Verma AD, Xia B (2012) CD4+ T cells: differentiation and functions. Clin Dev Immunol 2012:925135

    Article  PubMed  PubMed Central  Google Scholar 

  74. Gombart AF, Pierre A, Maggini S (2020) A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutrients 12:236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. MacGillivray DM, Kollmann TR (2014) The role of environmental factors in modulating immune responses in early life. Front Immunol 5:434

    Article  PubMed  PubMed Central  Google Scholar 

  76. Elmadfa I, Meyer AL (2019) The role of the status of selected micronutrients in shaping the immune function. Endocr Metab Immune Disord Drug Targets 19:1100–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Baumjohann D, Ansel KM (2013) MicroRNA-mediated regulation of T helper cell differentiation and plasticity. Nat Rev Immunol 13:666–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhang H-M, Kuang S, Xiong X, Gao T, Liu C, Guo A-Y (2015) Transcription factor and microRNA co-regulatory loops: important regulatory motifs in biological processes and diseases. Brief Bioinform 16:45–58

    Article  CAS  PubMed  Google Scholar 

  79. Hall JA, Pokrovskii M, Kroehling L, Kim B-R, Kim SY, Wu L, Lee J-Y, Littman DR (2022) Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element. Immunity 55(2027-2043):e2029

    Google Scholar 

  80. Forman JJ, Coller HA (2010) The code within the code: microRNAs target coding regions. Cell cycle 9:1533–1541

    Article  CAS  PubMed  Google Scholar 

  81. Yuan S, Tang C, Chen D, Li F, Huang M, Ye J, He Z, Li W et al (2019) miR-98 modulates cytokine production from human PBMCs in systemic lupus erythematosus by targeting IL-6 mRNA. J Immunol Res 2019:9827574

    Article  PubMed  PubMed Central  Google Scholar 

  82. Rom S, Dykstra H, Zuluaga-Ramirez V, Reichenbach NL, Persidsky Y (2015) miR-98 and let-7g* protect the blood-brain barrier under neuroinflammatory conditions. J Cereb Blood Flow Metab 35:1957–1965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bernstein DL, Zuluaga-Ramirez V, Gajghate S, Reichenbach NL, Polyak B, Persidsky Y, Rom S (2020) miR-98 reduces endothelial dysfunction by protecting blood–brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model. J Cereb Blood Flow Metab 40:1953–1965

    Article  CAS  PubMed  Google Scholar 

  84. Zhong L, Fu K, Xiao W, Wang F, Shen LL (2018) Overexpression of miR-98 attenuates neuropathic pain development via targeting STAT3 in CCI rat models. J Cell Biochem 120(5):7989–7799

    Article  PubMed  Google Scholar 

  85. Zhang Y, Su Z, An LJ, Li L, Wei M, Ge DJ, Liu HL (2019) miR-98 acts as an inhibitor in chronic constriction injury-induced neuropathic pain via downregulation of high-mobility group AT-hook 2. J Cell Biochem 120:10363–10369

    Article  CAS  PubMed  Google Scholar 

  86. Ting H-J, Messing J, Yasmin-Karim S, Lee Y-F (2013) Identification of microRNA-98 as a therapeutic target inhibiting prostate cancer growth and a biomarker induced by vitamin D. J Biol Chem 288:1–9

    Article  CAS  PubMed  Google Scholar 

  87. Banerjee S, Xie N, Cui H, Tan Z, Yang S, Icyuz M, Abraham E, Liu G (2013) MicroRNA let-7c regulates macrophage polarization. J Immunol 190:6542–6549

    Article  CAS  PubMed  Google Scholar 

  88. Jiang S, Yan W, Wang SE, Baltimore D (2018) Let-7 suppresses B cell activation through restricting the availability of necessary nutrients. Cell Metab 27(393-403):e394

    Google Scholar 

  89. Pobezinskaya EL, Wells AC, Angelou CC, Fagerberg E, Aral E, Iverson E, Kimura MY, Pobezinsky LA (2019) Survival of naïve T cells requires the expression of let-7 miRNAs. Front Immunol 10:955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Angelou CC, Wells AC, Vijayaraghavan J, Dougan CE, Lawlor R, Iverson E, Lazarevic V, Kimura MY et al (2020) Differentiation of pathogenic Th17 cells is negatively regulated by Let-7 microRNAs in a mouse model of multiple sclerosis. Front Immunol 10:3125

    Article  PubMed  PubMed Central  Google Scholar 

  91. Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC (2006) A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 203:1685–1691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Matsuki T, Nakae S, Sudo K, Horai R, Iwakura Y (2006) Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist system is responsible for the development of experimental autoimmune encephalomyelitis. Int Immunol 18:399–407

    Article  CAS  PubMed  Google Scholar 

  93. McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, McClanahan TK, O'shea JJ et al (2009) The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17–producing effector T helper cells in vivo. Nat Immunol 10:314–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192:899–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Gu SM, Park MH, Yun HM, Han SB, Oh KW, Son DJ, Yun JS, Hong JT (2016) CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice. Oncotarget 7:15382

    Article  PubMed  PubMed Central  Google Scholar 

  96. Guan H, Liu C, Chen Z, Wang L, Li C, Zhao J, Yu Y, Zhang P et al (2013) 1, 25-Dihydroxyvitamin D3 up-regulates expression of hsa-let-7a-2 through the interaction of VDR/VDRE in human lung cancer A549 cells. Gene 522:142–146

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors express their sincere gratitude to all the faculty members at Department of Immunology, School of Public Health, Tehran University of Medical Sciences, for their valuable discussions and contributions to this work.

Funding

This work was supported by research grants from the National Institute for Medical Research Development (NIMAD, grant No. 977636) and Tehran University of Medical Sciences (TUMS, grant No. 97-02-27 38998) and Iran National Science Foundation (INSF, grant No. 97005464). Dr Ali akbar Saboor-Yaraghi has received research support from all these centers. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Marziyeh Mohammadi-Kordkhayli, Fatemeh Mansouri & Ali Akbar Saboor-Yaraghi

  2. Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Alberta, Canada

    Marziyeh Mohammadi-Kordkhayli & Samira Ghorbani

  3. Sina MS Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Sahraian

  4. Immunoregulation Research Center, Shahed University, Tehran, Iran

    Farideh Talebi

  5. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Farshid Noorbakhsh

Authors
  1. Marziyeh Mohammadi-Kordkhayli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Ali Sahraian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samira Ghorbani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatemeh Mansouri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farideh Talebi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Farshid Noorbakhsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ali Akbar Saboor-Yaraghi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Marziyeh Mohammadi and Fatemeh provided reagents and prepared the materials. Farideh and Samira developed new software and analyzed the bioinformatics data. Marziyeh wrote the manuscript, and Dr. Farshid made revisions to the manuscript. All authors have read and approved the final manuscript.

All authors contributed to the study conception and design. Dr Ali akbar Saboor-Yaraghi and Dr Farshid Noorbakhsh supervised the study and Dr Mohammadi ali Sahraian served as adviser. Dr Ali akbar Saboor-Yaraghi, Dr Farshid Noorbakhsh, and Marziyeh Mohammadi kordkhayli designed experiments. Marziyeh Mohammadi kordkhayli performed experiments and data collection and analyzed and provided new tools. Fatemeh Mansouri provided reagents and prepared the material. Farideh Talebi and Samira Ghorbani developed new software and bioinformatics data. Marziyeh Mohammadi kordkhayli wrote the manuscript and Dr Ali akbar Saboor-Yaraghi and Dr Farshid Noorbakhsh made manuscript revisions. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Farshid Noorbakhsh or Ali Akbar Saboor-Yaraghi.

Ethics declarations

Competing Interests

Marziyeh Mohammadi, as a first author and PhD student, has received financial from Tehran University of Medical Sciences (TUMS) for this project, which represents her PhD project. Samira Ghorbani and Farideh Talebi have no financial interests associated with this work. Fatemeh Mansouri, as laboratory expert, has also received financial from TUMS. Dr. Ali akbar Saboor Yaraghi, Dr. Farshid Noorbakhsh, and Dr Mohammadali Sahraian as supervisors and adviser have received research funding from TUMS.

Ethics Approval

All experiments conducted in this study, “Vitamins A and D enhance the expression of Ror-γ-targeting miRNAs in a mouse model of multiple sclerosis”, as well as the animal care methods were approved by the Ethics Committee on Animal Experimentation of Tehran University of Medical Sciences The approval for this study was granted on July 18, 2018, with the approval reference number IR.TUMS.SPH.REC.1397.091.

Consent for Publication

The authors state that no human samples were utilized in this study. All samples utilized in this research were obtained from animals’ sources, specifically mice.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi-Kordkhayli, M., Sahraian, M.A., Ghorbani, S. et al. Vitamins A and D Enhance the Expression of Ror-γ-Targeting miRNAs in a Mouse Model of Multiple Sclerosis. Mol Neurobiol 60, 5853–5865 (2023). https://doi.org/10.1007/s12035-023-03427-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-023-03427-3

Keywords

Search

Navigation