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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Anti-Inflammatory &amp; Anti-Allergy Agents in Medicinal Chemistry</journal-id><journal-title-group><journal-title xml:lang="en">Anti-Inflammatory &amp; Anti-Allergy Agents in Medicinal Chemistry</journal-title><trans-title-group xml:lang="ru"><trans-title>Anti-Inflammatory &amp; Anti-Allergy Agents in Medicinal Chemistry</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1871-5230</issn><issn publication-format="electronic">1875-614X</issn><publisher><publisher-name xml:lang="en">Bentham Science</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">644660</article-id><article-id pub-id-type="doi">10.2174/0118715230293847240314073359</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>Medicine</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Fasihi</surname><given-names>Mahdieh</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Samimi-Badabi</surname><given-names>Mahsa</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Robat-Jazi</surname><given-names>Behrouz</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Bitarafan</surname><given-names>Sama</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Moghadasi</surname><given-names>Abdorreza</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name><surname>Mansouri</surname><given-names>Fatemeh</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Yekaninejad</surname><given-names>Mir</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><name><surname>Izad</surname><given-names>Maryam</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff5"/></contrib><contrib contrib-type="author"><name><surname>Saboor-Yaraghi</surname><given-names>Ali</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff id="aff1"><institution>Department of Immunology, School of Public Health, Tehran University of Medical Sciences</institution></aff><aff id="aff2"><institution>Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences</institution></aff><aff id="aff3"><institution>Department of Neurology and MS Research Center, Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences</institution></aff><aff id="aff4"><institution>Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences</institution></aff><aff id="aff5"><institution>Department of Immunology, School of Medicine, Tehran University of Medical Sciences</institution></aff><pub-date date-type="pub" iso-8601-date="2024-02-01" publication-format="electronic"><day>01</day><month>02</month><year>2024</year></pub-date><volume>23</volume><issue>2</issue><issue-title xml:lang="ru"/><fpage>138</fpage><lpage>147</lpage><history><date date-type="received" iso-8601-date="2025-01-07"><day>07</day><month>01</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Bentham Science Publishers</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Bentham Science Publishers</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://journals.eco-vector.com/1871-5230/article/view/644660">https://journals.eco-vector.com/1871-5230/article/view/644660</self-uri><abstract xml:lang="en"><p id="idm46041443632448">Objectives:Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS.</p><p id="idm46041443636448">Methods:PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 µg/mL of calcitriol and 10 µg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomod-ulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry.</p><p id="idm46041443640416">Results:Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, including IFN-γ, T-bet, IL-17, and RORC. Furthermore, the frequency of these cells decreased following treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregulation of the FOXP3 gene expression and an increase in the frequency of Treg cells.</p><p id="idm46041443645472">Conclusion:This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.</p></abstract><kwd-group xml:lang="en"><kwd>Multiple sclerosis</kwd><kwd>calcitriol</kwd><kwd>curcumin</kwd><kwd>Th1</kwd><kwd>Th17</kwd><kwd>Treg.</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Chakamian, K.; Jazi, R.B.; Moghadasi, A.N.; Mansouri, F.; Nodehi, M.; Motevaseli, E.; Izad, M.; Yekaninejad, S.; Shirzad, M.; Bidad, K.; Oraei, M.; Ansaripour, B.; Yaraghi, S.A.A. Immunosuppressive effects of two probiotics, lactobacillus paracasei DSM 13434 and lactobacillus plantarum DSM 15312, on CD4+ T cells of multiple sclerosis patients. Iran. J. Allergy Asthma Immunol., 2023, 22(1), 34-45. doi: 10.18502/ijaai.v22i1.12004 PMID: 37002629</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Robat-Jazi, B.; Oraei, M.; Bitarafan, S.; Namin, M.S.A.; Zadeh, N.A.; Mansouri, F.; Parastouei, K.; Anissian, A.; Yekaninejad, M.S.; Yaraghi, S.A.A. Immunoregulatory effect of calcitriol on experimental autoimmune encephalomyelitis (EAE) mice. Iran. J. Allergy Asthma Immunol., 2023, 22(5), 452-467. PMID: 38085147</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Kubick, N.; Lazarczyk, M.; Strzałkowska, N.; Charuta, A.; Horbańczuk, J.O.; Sacharczuk, M.; Mickael, M.E. Factors regulating the differences in frequency of infiltration of Th17 and Treg of the bloodbrain barrier. Immunogenetics, 2023, 75(5), 417-423. doi: 10.1007/s00251-023-01310-y PMID: 37430007</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Rostami, A.; Ciric, B. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination. J. Neurol. Sci., 2013, 333(1-2), 76-87. doi: 10.1016/j.jns.2013.03.002 PMID: 23578791</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Sakaguchi, S.; Ono, M.; Setoguchi, R.; Yagi, H.; Hori, S.; Fehervari, Z.; Shimizu, J.; Takahashi, T.; Nomura, T. Foxp3 + CD25 + CD4 + natural regulatory T cells in dominant self‐tolerance and autoimmune disease. Immunol. Rev., 2006, 212(1), 8-27. doi: 10.1111/j.0105-2896.2006.00427.x PMID: 16903903</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Costantino, C.M.; Allan, B.C.; Hafler, D.A. Multiple sclerosis and regulatory T cells. J. Clin. Immunol., 2008, 28(6), 697-706. doi: 10.1007/s10875-008-9236-x PMID: 18763026</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Venken, K.; Hellings, N.; Thewissen, M.; Somers, V.; Hensen, K.; Rummens, J.L.; Medaer, R.; Hupperts, R.; Stinissen, P. Compromised CD4 + CD25 high regulatory T‐cell function in patients with relapsing‐remitting multiple sclerosis is correlated with a reduced frequency of FOXP3‐positive cells and reduced FOXP3 expression at the single‐cell level. Immunology, 2008, 123(1), 79-89. doi: 10.1111/j.1365-2567.2007.02690.x PMID: 17897326</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Amalraj, A.; Pius, A.; Gopi, S.; Gopi, S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives  A review. J. Tradit. Complement. Med., 2017, 7(2), 205-233. doi: 10.1016/j.jtcme.2016.05.005 PMID: 28417091</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Ahmad, R.S.; Hussain, M.B.; Sultan, M.T.; Arshad, M.S.; Waheed, M.; Shariati, M.A.; Plygun, S.; Hashempur, M.H. Biochemistry, safety, pharmacological activities, and clinical applications of turmeric: A mechanistic review. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-14. doi: 10.1155/2020/7656919 PMID: 32454872</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Kocaadam, B.; Şanlier, N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit. Rev. Food Sci. Nutr., 2017, 57(13), 2889-2895. doi: 10.1080/10408398.2015.1077195 PMID: 26528921</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Xie, L.; Li, X.K.; Takahara, S. Curcumin has bright prospects for the treatment of multiple sclerosis. Int. Immunopharmacol., 2011, 11(3), 323-330. doi: 10.1016/j.intimp.2010.08.013 PMID: 20828641</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Lee, W.H.; Loo, C.Y.; Bebawy, M.; Luk, F.; Mason, R.; Rohanizadeh, R. Curcumin and its derivatives: Their application in neuropharmacology and neuroscience in the 21st century. Curr. Neuropharmacol., 2013, 11(4), 338-378. doi: 10.2174/1570159X11311040002 PMID: 24381528</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Yang, C.Y.; Leung, P.S.C.; Adamopoulos, I.E.; Gershwin, M.E. The implication of vitamin D and autoimmunity: A comprehensive review. Clin. Rev. Allergy Immunol., 2013, 45(2), 217-226. doi: 10.1007/s12016-013-8361-3 PMID: 23359064</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Robat-Jazi, B.; Mobini, S.; Chahardoli, R.; Mansouri, F.; Nodehi, M.; Esfahanian, F.; Yaraghi, S.A.A. The impact of vitamin D supplementation on the IFNγ-IP10 axis in women with hashimotos thyroiditis treated with levothyroxine: A double-blind randomized placebo-controlled trial. Iran. J. Allergy Asthma Immunol., 2022, 21(4), 407-417. doi: 10.18502/ijaai.v21i4.10288 PMID: 36243929</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Aranow, C. Vitamin D and the immune system. J. Investig. Med., 2011, 59(6), 881-886. doi: 10.2310/JIM.0b013e31821b8755 PMID: 21527855</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Bouillon, R.; Carmeliet, G.; Verlinden, L.; van Etten, E.; Verstuyf, A.; Luderer, H.F.; Lieben, L.; Mathieu, C.; Demay, M. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr. Rev., 2008, 29(6), 726-776. doi: 10.1210/er.2008-0004 PMID: 18694980</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Robat-Jazi, B.; Hosseini, M.; Shaygannejad, V.; Nafissi, S.; Rezaei, A.; Mansourain, M.; Mirmosayyeb, O.; Esmaeil, N. High frequency of Tc22 and Th22 cells in myasthenia gravis patients and their significant reduction after thymectomy. Neuroimmunomodulation, 2018, 25(2), 80-88. doi: 10.1159/000490855 PMID: 30071533</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Hosseini, M.; Jazi, R.B.; Shaygannejad, V.; Naffisi, S.; Mirmossayeb, O.; Rezaei, A.; Mansourian, M.; Esmaeil, N. Increased proportion of Tc17 and Th17 cells and their significant reduction after thymectomy may be related to disease progression in myasthenia gravis. Neuroimmunomodulation, 2017, 24(4-5), 264-270. doi: 10.1159/000486037 PMID: 29414833</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Tryfonos, C.; Mantzorou, M.; Fotiou, D.; Vrizas, M.; Vadikolias, K.; Pavlidou, E.; Giaginis, C. Dietary supplements on controlling multiple sclerosis symptoms and relapses: Current clinical evidence and future perspectives. Medicines , 2019, 6(3), 95. doi: 10.3390/medicines6030095 PMID: 31547410</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Gauzzi, M.C. Vitamin D-binding protein and multiple sclerosis: Evidence, controversies, and needs. Mult. Scler., 2018, 24(12), 1526-1535. doi: 10.1177/1352458518792433 PMID: 30113253</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Jagannath, V.A.; Filippini, G.; Di Pietrantonj, C.; Asokan, G.V.; Robak, E.W.; Whamond, L.; Robinson, S.A. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst. Rev., 2018, 9(9)CD008422 PMID: 30246874</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Dobson, R.; Cock, H.R.; Brex, P.; Giovannoni, G. Vitamin D supplementation. Pract. Neurol., 2018, 18(1), 35-42. doi: 10.1136/practneurol-2017-001720 PMID: 28947637</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Sintzel, M.B.; Rametta, M.; Reder, A.T. Vitamin D and multiple sclerosis: A comprehensive review. Neurol. Ther., 2018, 7(1), 59-85. doi: 10.1007/s40120-017-0086-4 PMID: 29243029</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Smolders, J.; Torkildsen, Ø.; Camu, W.; Holmøy, T. An update on vitamin D and disease activity in multiple sclerosis. CNS Drugs, 2019, 33(12), 1187-1199. doi: 10.1007/s40263-019-00674-8 PMID: 31686407</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Zhang, X.; Ge, R.; Chen, H.; Ahiafor, M.; Liu, B.; Chen, J.; Fan, X. Follicular helper CD4+ T cells, follicular regulatory CD4+ T cells, and inducible costimulator and their roles in multiple sclerosis and experimental autoimmune encephalomyelitis. Mediators Inflamm., 2021, 2021, 1-10. doi: 10.1155/2021/2058964 PMID: 34552387</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Wing, J.B.; Tanaka, A.; Sakaguchi, S. Human FOXP3+ regulatory T cell heterogeneity and function in autoimmunity and cancer. Immunity, 2019, 50(2), 302-316. doi: 10.1016/j.immuni.2019.01.020 PMID: 30784578</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Scheinecker, C.; Göschl, L.; Bonelli, M. Treg cells in health and autoimmune diseases: New insights from single cell analysis. J. Autoimmun., 2020, 110102376 doi: 10.1016/j.jaut.2019.102376 PMID: 31862128</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Sun, C.M.; Hall, J.A.; Blank, R.B.; Bouladoux, N.; Oukka, M.; Mora, J.R.; Belkaid, Y. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med., 2007, 204(8), 1775-1785. doi: 10.1084/jem.20070602 PMID: 17620362</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Huan, J.; Culbertson, N.; Spencer, L.; Bartholomew, R.; Burrows, G.G.; Chou, Y.K.; Bourdette, D.; Ziegler, S.F.; Offner, H.; Vandenbark, A.A. Decreased FOXP3 levels in multiple sclerosis patients. J. Neurosci. Res., 2005, 81(1), 45-52. doi: 10.1002/jnr.20522 PMID: 15952173</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Libera, D.D.; Di Mitri, D.; Bergami, A.; Centonze, D.; Gasperini, C.; Grasso, M.G.; Galgani, S.; Martinelli, V.; Comi, G.; Avolio, C.; Martino, G.; Borsellino, G.; Sallusto, F.; Battistini, L.; Furlan, R. T regulatory cells are markers of disease activity in multiple sclerosis patients. PLoS One, 2011, 6(6)e21386 doi: 10.1371/journal.pone.0021386 PMID: 21731726</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Sakaguchi, S.; Yamaguchi, T.; Nomura, T.; Ono, M. Regulatory T cells and immune tolerance. Cell, 2008, 133(5), 775-787. doi: 10.1016/j.cell.2008.05.009 PMID: 18510923</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Fontenot, J.D.; Gavin, M.A.; Rudensky, A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol., 2003, 4(4), 330-336. doi: 10.1038/ni904 PMID: 12612578</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Hori, S.; Nomura, T.; Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science, 2003, 299(5609), 1057-1061. doi: 10.1126/science.1079490 PMID: 12522256</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Khattri, R.; Cox, T.; Yasayko, S.A.; Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol., 2003, 4(4), 337-342. doi: 10.1038/ni909 PMID: 12612581</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Deng, G.; Song, X.; Fujimoto, S.; Piccirillo, C.A.; Nagai, Y.; Greene, M.I. Foxp3 post-translational modifications and treg suppressive activity. Front. Immunol., 2019, 10, 2486. doi: 10.3389/fimmu.2019.02486 PMID: 31681337</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>von Knethen, A.; Heinicke, U.; Weigert, A.; Zacharowski, K.; Brüne, B. Histone deacetylation inhibitors as modulators of regulatory T cells. Int. J. Mol. Sci., 2020, 21(7), 2356. doi: 10.3390/ijms21072356 PMID: 32235291</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Palomares, O.; Elewaut, D.; Irving, P.M.; Jaumont, X.; Tassinari, P. Regulatory T cells and immunoglobulin E: A new therapeutic link for autoimmunity? Allergy, 2022, 77(11), 3293-3308. doi: 10.1111/all.15449 PMID: 35852798</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Danikowski, K.M.; Jayaraman, S.; Prabhakar, B.S. Regulatory T cells in multiple sclerosis and myasthenia gravis. J. Neuroinflammation, 2017, 14(1), 117. doi: 10.1186/s12974-017-0892-8 PMID: 28599652</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Viglietta, V.; Baecher-Allan, C.; Weiner, H.L.; Hafler, D.A. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med., 2004, 199(7), 971-979. doi: 10.1084/jem.20031579 PMID: 15067033</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Haas, J.; Hug, A.; Viehöver, A.; Fritzsching, B.; Falk, C.S.; Filser, A.; Vetter, T.; Milkova, L.; Korporal, M.; Fritz, B.; Hagenlocher, S.B.; Krammer, P.H.; Suri-Payer, E.; Wildemann, B. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol., 2005, 35(11), 3343-3352. doi: 10.1002/eji.200526065 PMID: 16206232</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Moser, T.; Akgün, K.; Proschmann, U.; Sellner, J.; Ziemssen, T. The role of TH17 cells in multiple sclerosis: Therapeutic implications. Autoimmun. Rev., 2020, 19(10)102647 doi: 10.1016/j.autrev.2020.102647 PMID: 32801039</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Kamali, A.N.; Noorbakhsh, S.M.; Hamedifar, H.; Niaragh, J.F.; Yazdani, R.; Bautista, J.M.; Azizi, G. A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders. Mol. Immunol., 2019, 105, 107-115. doi: 10.1016/j.molimm.2018.11.015 PMID: 30502718</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Melnikov, M.; Lopatina, A. Th17-cells in depression: Implication in multiple sclerosis. Front. Immunol., 2022, 131010304 doi: 10.3389/fimmu.2022.1010304 PMID: 36189272</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Melnikov, M.; Rogovskii, V.; Boyko, A.; Pashenkov, M. Dopaminergic therapeutics in multiple sclerosis: Focus on Th17-cell functions. J. Neuroimmune Pharmacol., 2020, 15(1), 37-47. doi: 10.1007/s11481-019-09852-3 PMID: 31011885</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Yang, J.; Sundrud, M.S.; Skepner, J.; Yamagata, T. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol. Sci., 2014, 35(10), 493-500. doi: 10.1016/j.tips.2014.07.006 PMID: 25131183</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Kumar, R.; Theiss, A.L.; Venuprasad, K. RORγt protein modifications and IL-17-mediated inflammation. Trends Immunol., 2021, 42(11), 1037-1050. doi: 10.1016/j.it.2021.09.005 PMID: 34635393</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Balasa, R.; Barcutean, L.; Balasa, A.; Motataianu, A.; Filip, R.C.; Manu, D. The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum. Immunol., 2020, 81(5), 237-243. doi: 10.1016/j.humimm.2020.02.009 PMID: 32122685</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Ntolkeras, G.; Barba, C.; Mavropoulos, A.; Vasileiadis, G.K.; Dardiotis, E.; Sakkas, L.I.; Hadjigeorgiou, G.; Bogdanos, D.P. On the immunoregulatory role of statins in multiple sclerosis: the effects on Th17 cells. Immunol. Res., 2019, 67(4-5), 310-324. doi: 10.1007/s12026-019-09089-5 PMID: 31399952</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Melnikov, M.; Rogovskii, V.; Boyko, A.; Pashenkov, M. The influence of biogenic amines on Th17-mediated immune response in multiple sclerosis. Mult. Scler. Relat. Disord., 2018, 21, 19-23. doi: 10.1016/j.msard.2018.02.012 PMID: 29454152</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>McGinley, A.M.; Edwards, S.C.; Raverdeau, M.; Mills, K.H.G. Th17 cells, γδ T cells and their interplay in EAE and multiple sclerosis. J. Autoimmun., 2018, 87, 97-108. doi: 10.1016/j.jaut.2018.01.001 PMID: 29395738</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Melnikov, M.; Pashenkov, M.; Boyko, A. Dopaminergic receptor targeting in multiple sclerosis: Is there therapeutic potential? Int. J. Mol. Sci., 2021, 22(10), 5313. doi: 10.3390/ijms22105313 PMID: 34070011</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Chen, C.; Zhou, Y.; Wang, J.; Yan, Y.; Peng, L.; Qiu, W. Dysregulated MicroRNA involvement in multiple sclerosis by induction of T helper 17 cell differentiation. Front. Immunol., 2018, 9, 1256. doi: 10.3389/fimmu.2018.01256 PMID: 29915595</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Joshi, S.; Pantalena, L.C.; Liu, X.K.; Gaffen, S.L.; Liu, H.; Kochan, C.; Ichiyama, K.; Yoshimura, A.; Steinman, L.; Christakos, S.; Youssef, S. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol. Cell. Biol., 2011, 31(17), 3653-3669. doi: 10.1128/MCB.05020-11 PMID: 21746882</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Zeitelhofer, M.; Adzemovic, M.Z.; Cabrero, G.D.; Bergman, P.; Hochmeister, S.; Ndiaye, M.; Paulson, A.; Ruhrmann, S.; Almgren, M.; Tegnér, J.N.; Ekström, T.J.; Cacais, G.A.O.; Jagodic, M. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci., 2017, 114(9), E1678-E1687. doi: 10.1073/pnas.1615783114 PMID: 28196884</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Mahler, J.V.; Solti, M.; Pereira, A.S.L.; Adoni, T.; Silva, G.D.; Callegaro, D. Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials. Mult. Scler. Relat. Disord., 2024, 82105433 doi: 10.1016/j.msard.2024.105433 PMID: 38211504</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Butzkueven, H.; Ponsonby, A.L.; Stein, M.S.; Lucas, R.M.; Mason, D.; Broadley, S.; Kilpatrick, T.; Scott, L.J.; Barnett, M.; Carroll, W.; Mitchell, P.; Hardy, T.A.; Macdonell, R.; McCombe, P.; Lee, A.; Kalincik, T.; van der Walt, A.; Lynch, C.; Abernethy, D.; Willoughby, E.; Barkhof, F.; MacManus, D.; Clarke, M.; Andrew, J.; Morahan, J.; Zhu, C.; Dear, K.; Taylor, B.V. Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome. Brain, 2023, 2023awad409 doi: 10.1093/brain/awad409 PMID: 38085047</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Cassard, S.D.; Fitzgerald, K.C.; Qian, P.; Emrich, S.A.; Azevedo, C.J.; Goodman, A.D.; Sugar, E.A.; Pelletier, D.; Waubant, E.; Mowry, E.M. High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: A randomised clinical trial. EClinicalMedicine, 2023, 59101957 doi: 10.1016/j.eclinm.2023.101957 PMID: 37125397</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Handono, K.; Pratama, M.Z.; Endharti, A.T.; Kalim, H. Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+ T cell cultures of systemic lupus erythematosus patients. Cent. Eur. J. Immunol., 2015, 4(4), 461-469. doi: 10.5114/ceji.2015.56970 PMID: 26862311</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Liu, X.; Lee, Y.S.; Yu, C.R.; Egwuagu, C.E. Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases. J. Immunol., 2008, 180(9), 6070-6076. doi: 10.4049/jimmunol.180.9.6070 PMID: 18424728</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Kim, H.Y.; Park, E.J.; Joe, E.; Jou, I. Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J. Immunol., 2003, 171(11), 6072-6079. doi: 10.4049/jimmunol.171.11.6072 PMID: 14634121</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Xie, L.; Li, X.K.; Fuji, F.N.; Kimura, H.; Matsumoto, Y.; Isaka, Y.; Takahara, S. Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int. Immunopharmacol., 2009, 9(5), 575-581. doi: 10.1016/j.intimp.2009.01.025 PMID: 19539560</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Bharti, A.C.; Donato, N.; Aggarwal, B.B. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J. Immunol., 2003, 171(7), 3863-3871. doi: 10.4049/jimmunol.171.7.3863 PMID: 14500688</mixed-citation></ref></ref-list></back></article>
