4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

          Related collections

          Most cited references118

          • Record: found
          • Abstract: found
          • Article: not found

          Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

          The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Induction of intestinal Th17 cells by segmented filamentous bacteria.

            The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. How commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4(+) T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation and antimicrobial defenses and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Thus, manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43.

              The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases. One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in 'healthy' microbiota such as Bifidobacterium and Bacteriodes, and a concurrent reduction in SCFAs. Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis. SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43(-/-) immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
                Bookmark

                Author and article information

                Contributors
                On behalf of : on behalf of SIGR
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                28 February 2021
                March 2021
                : 22
                : 5
                : 2456
                Affiliations
                [1 ]Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, 00184 Rome, Italy; cpagnini@ 123456hsangiovanni.roma.it
                [2 ]Department of Clinical and Molecular Medicine, S. Andrea University Hospital, Sapienza University, 00189 Rome, Italy; bruno.lagana@ 123456uniroma1.it
                [3 ]Department of Internal Medicine, Rheumatology and Gastroenterology, Nuovo Regina Margherita Hospital, 00153 Rome, Italy; vinbruzzese@ 123456tiscali.it (V.B.); rlorenzetti2004@ 123456yahoo.it (R.L.); palma.scolieri@ 123456gmail.com (P.S.)
                [4 ]Clinica Medica, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, 60131 Ancona, Italy; m.luchetti@ 123456staff.univpm.it
                [5 ]Ospedale Regina Apostolorum, U.O. di Medicina Interna e Reumatologia, 00041 Albano Laziale, Italy; severino.martin@ 123456gmail.com
                [6 ]Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, 00157 Rome, Italy; robertapica5@ 123456gmail.com
                [7 ]Gastroenterology Unit, AO San Camillo Forlanini, 00152 Rome, Italy; marialiascribano@ 123456virgilio.it
                [8 ]Division of Gastroenterology, Belcolle Hospital, 01100 Viterbo, Italy; zcosta@ 123456libero.it
                [9 ]Rheumatology, Allergology and Clinical Immunology, Department of Medicina dei Sistemi, University of Rome Tor Vergata, 00187 Rome, Italy; maria.sole.chimenti@ 123456uniroma2.it
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-9985-7490
                https://orcid.org/0000-0002-8552-4641
                https://orcid.org/0000-0001-7342-6350
                https://orcid.org/0000-0003-2130-4321
                https://orcid.org/0000-0002-1097-9430
                https://orcid.org/0000-0002-2055-7282
                https://orcid.org/0000-0003-1839-8136
                https://orcid.org/0000-0002-1343-1729
                https://orcid.org/0000-0003-2305-4063
                Article
                ijms-22-02456
                10.3390/ijms22052456
                7957646
                33671090
                99a6d0c4-8e85-4537-ba27-85c5afcac9ac
                © 2021 by the authors.

                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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 February 2021
                : 24 February 2021
                Categories
                Review

                Molecular biology
                osteoimmunology,inflammatory bowel diseases,spondyloarthritis,microbiota,intestinal mucosal barrier,vitamin d,vitamin d receptor,immunomodulation

                Comments

                Comment on this article