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It can suppress inflammation and promote tolerogenic immune responses.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which autoimmune diseases are discussed as being associated with vitamin D insufficiency or deficiency?",{"text":68,"@type":64},"The review discusses multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus, linking vitamin D insufficiency or deficiency to disease pathogenesis and/or activity.",{"name":70,"@type":61,"acceptedAnswer":71},"What role is vitamin D proposed to play in gastrointestinal autoimmune disorders like IBD and celiac disease?",{"text":72,"@type":64},"The text explains that chronic intestinal inflammation can lead to malabsorption, contributing to vitamin D deficiency. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; [federica.vincenzi@uniupo.it](federica.vincenzi@uniupo.it) (F.V.); [stelvio.tonello@med.uniupo.it](stelvio.tonello@med.uniupo.it) (S.T.); [pierpaolo.sainaghi@med.uniupo.it](pierpaolo.sainaghi@med.uniupo.it) (P.P.S.)  \n2 Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, 28100 Novara, Italy  \n* Correspondence: [carlo.smirne@med.uniupo.it](carlo.smirne@med.uniupo.it)[ ](carlo.smirne@med.uniupo.it)† These authors contributed equally to this work.  \nAbstract  \nVitamin D is a steroid hormone whose relevant immunomodulatory role has been widely described. Therefore, its contribution to the pathogenesis of immune-mediated diseases isan important and ongoing matter of research. Specifically, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with its receptor, exerts different activities on the innate and adaptive immune system, among which are suppression of inflammation and promotion of tolerogenic responses. Indeed, vitamin D insufficiency/deficiency has been related to the pathogenesis and/or disease activity of several autoimmune diseases, including, amongst others, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus. Based on these premises, in this review, we will describe the main molecular mechanisms modulated by vitamin D in the regulation of immune responses, including the induction of immune tolerance. Moreover, we will focus on the current knowledge regarding the contribution of vitamin D depletion to the aforementioned autoimmune diseases, seeking to provide evidence as to why its supplementation in the context of these immune-mediated disorders may potentially ameliorate disease activity and its related clinical manifestations.  \nKeywords: vitamin D; immune system; autoimmune diseases; autoimmunity; cholecalciferol; calcitriol; rheumatoid arthritis; multiple sclerosis; systemic lupus erythematosus; type 1 diabetes mellitus  \n1. Introduction  \nVitamin D is a fat-soluble vitamin mainly involved in bone remodeling, through the regulation of calcium reabsorption from bone and intestine. Due to its structure, vitamin D acts as a hormone, influencing cellular differentiation and proliferation, immune system regulation, neural function, and cardiovascular health [1] . Despite its classical function, increasing evidence has been gathered on the immunomodulatory effects of vitamin D on both innate and adaptive immune systems. This knowledge arises from studies performed in 1903 by Dr. Nils Filsen, who cured the epidermal form of tuberculosis (lupus vulgaris) using light irradiation. The following findings regarding the synthesis of vitamin D in the skin after ultraviolet (UV) light exposure opened a window to the possible immunomodulatory role of vitamin D, particularly in the treatment of mycobacterial infections, such as tuberculosis and leprosy [2] . Further studies showed that both vitamin D receptor (VDR) and metabolizing enzymes are expressed in a plethora of immune cells,  \nincluding dendritic cells, lymphocytes, monocytes, and macrophages. These findings highlight the capacity of immune cells to synthetize vitamin D, producing both VDRmediated paracrine or intracrine responses [2] . In light of the current knowledge about vitamin D’s immunomodulatory role, researchers focused on the possible contribut","cbCailAOJyU95EpV","https://ap.wps.com/l/cbCailAOJyU95EpV","pdf",965116,28,"English","# Introduction\n## Vitamin D as a hormone and immunomodulator\n## Evidence linking vitamin D deficiency to autoimmunity\n## Broader autoimmune conditions beyond major diseases","[{\"question\":\"How does active vitamin D influence immune responses in autoimmune diseases?\",\"answer\":\"Active vitamin D (1,25-dihydroxyvitamin D) interacts with its receptor to modulate innate and adaptive immunity. It can suppress inflammation and promote tolerogenic immune responses.\"},{\"question\":\"Which autoimmune diseases are discussed as being associated with vitamin D insufficiency or deficiency?\",\"answer\":\"The review discusses multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus, linking vitamin D insufficiency or deficiency to disease pathogenesis and/or activity.\"},{\"question\":\"What role is vitamin D proposed to play in gastrointestinal autoimmune disorders like IBD and celiac disease?\",\"answer\":\"The text explains that chronic intestinal inflammation can lead to malabsorption, contributing to vitamin D deficiency. Vitamin D/VDR signaling may also affect intestinal barrier function, antimicrobial peptide release, and mucus secretion, while supplementation evidence for celiac disease is noted as inconclusive.\"}]","The Role of Vitamin D in Autoimmune Diseases - Review | PDF",1790765126,71]