{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:33:32Z","timestamp":1781822012426,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about the mechanisms underlying this anti-inflammatory effect and the potential sex differences of calcitriol immune regulation. Hence, the aim of this study was to investigate whether calcitriol could act differently in modulating T cell immunity of age-matched male and female healthy donors. We analyzed the effects of calcitriol in T lymphocytes from healthy women and men on the expression levels of the vitamin D receptor (VDR) and pro- and anti-inflammatory cytokine production. We showed that a treatment with calcitriol induced a significant increase in the VDR expression levels of activated T lymphocytes from male and female healthy subjects. Moreover, we found that calcitriol significantly reduced the expression level of pro-inflammatory cytokines IL-17, INF-\u03b3 and TNF-\u03b1 in the T lymphocytes of both sexes. Notably, we observed that calcitriol induced a significant increase in the expression level of anti-inflammatory cytokine IL-10 only in the T lymphocytes from female healthy donors. In conclusion, our study provides new insights regarding the sex-specific anti-inflammatory role of calcitriol in T cell immunity.<\/jats:p>","DOI":"10.3390\/ijms23169164","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:58:08Z","timestamp":1660597088000},"page":"9164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Anti-Inflammatory Effects of 1,25(OH)2D\/Calcitriol in T Cell Immunity: Does Sex Make a Difference?"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7852-2739","authenticated-orcid":false,"given":"Daniela","family":"Peruzzu","sequence":"first","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Pierdominici","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Fecchi","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ortona","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9215-9187","authenticated-orcid":false,"given":"Maria Teresa","family":"Pagano","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Medicine, Istituto Superiore di Sanit\u00e0, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1515\/jpem-2017-0391","article-title":"Vitamin D deficiency in childhood: Old lessons and current challenges","volume":"31","author":"Antonucci","year":"2018","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_2","unstructured":"World Health Organization (2005). Vitamin and Mineral Requirements in Human Nutrition, World Health Organization. [2nd ed.]. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/42716."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"38084","DOI":"10.1074\/jbc.M307028200","article-title":"De-orphanization of cytochrome P450 2R1: A microsomal vitamin D 25-hydroxilase","volume":"278","author":"Cheng","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"491S","DOI":"10.1093\/ajcn\/88.2.491S","article-title":"From vitamin D to hormone D: Fundamentals of the vitamin D endocrine system essential for good health","volume":"88","author":"Norman","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Carlberg, C. (2022). Vitamin D in the Context of Evolution. Nutrients, 14.","DOI":"10.3390\/nu14153018"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13293-021-00358-3","article-title":"The role of vitamin D in autoimmune diseases: Could sex make the difference?","volume":"12","author":"Dupuis","year":"2021","journal-title":"Biol. Sex Differ."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rochel, N. (2022). Vitamin D and Its Receptor from a Structural Perspective. Nutrients, 14.","DOI":"10.3390\/nu14142847"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"398","DOI":"10.7326\/M13-1788","article-title":"Association of dietary, circulating, and supplement fatty acids with coronary risk: A systematic review and meta-analysis","volume":"160","author":"Chowdhury","year":"2014","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1378\/chest.128.6.3792","article-title":"Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey","volume":"128","author":"Black","year":"2005","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jaci.2007.08.028","article-title":"Is vitamin D deficiency to blame for the asthma epidemic?","volume":"120","author":"Litonjua","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/ejcn.2011.118","article-title":"Vitamin D and type 2 diabetes: A systematic review","volume":"65","author":"Mitri","year":"2011","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102350","DOI":"10.1016\/j.autrev.2019.102350","article-title":"Emerging role of vitamin D in autoimmune diseases: An update on evidence and therapeutic implications","volume":"18","author":"Murdaca","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bellan, M., Andreoli, L., Mele, C., Sainaghi, P.P., Rigamonti, C., Piantoni, S., De Benedittis, C., Aimaretti, G., Pirisi, M., and Marzullo, P. (2020). Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases. Nutrients, 12.","DOI":"10.3390\/nu12030789"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s00223-019-00577-2","article-title":"Vitamin D, Autoimmune Disease and Rheumatoid Arthritis","volume":"106","author":"Harrison","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/aje\/kwq113","article-title":"Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers","volume":"172","author":"McCullough","year":"2010","journal-title":"Am. J. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00198-008-0626-y","article-title":"Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: An ecologic meta-regression analysis","volume":"20","author":"Hagenau","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1743-7075-12-2","article-title":"Sex-specific determinants of serum 25-hydroxyvitamin D3 concentrations in an elderly German cohort: A cross-sectional study","volume":"12","author":"Jungert","year":"2015","journal-title":"Nutr. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.4049\/jimmunol.1000588","article-title":"Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects","volume":"185","author":"Correale","year":"2010","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jneuroim.2015.06.015","article-title":"Vitamin D and estrogen synergy in Vdr-expressing CD4(+) T cells is essential to induce Helios(+)FoxP3(+) T cells and prevent autoimmune demyelinating disease","volume":"286","author":"Spanier","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1172\/JCI113915","article-title":"Effects of estrogen on circulating \u201cfree\u201d and total 1,25-dihydroxyvitamin D and on the parathyroid-vitamin D axis in postmenopausal women","volume":"83","author":"Cheema","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.bbalip.2011.01.004","article-title":"1alpha,25-Dihydroxyvitamin D3 exerts tissue-specific effects on estrogen and androgen metabolism","volume":"1811","author":"Lundqvist","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1128\/MCB.19.2.1049","article-title":"Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog","volume":"19","author":"Takeyama","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3389\/fphys.2014.00151","article-title":"Impact of vitamin D on immune function: Lessons learned from genome-wide analysis","volume":"5","author":"Chun","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1210\/jc.2009-1773","article-title":"Update in vitamin D","volume":"95","author":"Adams","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Charoenngam, N., and Holick, M.F. (2020). Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients, 12.","DOI":"10.3390\/nu12072097"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.4049\/jimmunol.0803217","article-title":"1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3","volume":"183","author":"Jeffery","year":"2009","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Martens, P.J., Gysemans, C., Verstuyf, A., and Mathieu, A.C. (2020). Vitamin D\u2019s Effect on Immune Function. Nutrients, 12.","DOI":"10.3390\/nu12051248"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Crescioli, C. (2021). The Role of Estrogens and Vitamin D in Cardiomyocyte Protection: A Female Perspective. Biomolecules, 11.","DOI":"10.3390\/biom11121815"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e12799","DOI":"10.1111\/jne.12799","article-title":"Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer","volume":"32","author":"Norlin","year":"2020","journal-title":"J. Neuroendocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1210\/jc.2016-1658","article-title":"Use of Estrogen-Containing Contraception Is Associated with Increased Concentrations of 25-Hydroxy Vitamin D","volume":"101","author":"Harmon","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.maturitas.2016.11.017","article-title":"Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"96","author":"Zhao","year":"2017","journal-title":"Maturitas"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.imlet.2010.06.003","article-title":"Estrogen receptor profiles in human peripheral blood lymphocytes","volume":"132","author":"Pierdominici","year":"2010","journal-title":"Immunol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:09:01Z","timestamp":1760141341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":32,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23169164"],"URL":"https:\/\/doi.org\/10.3390\/ijms23169164","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}