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Nutrients
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Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition)
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Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition)

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (25 October 2024) | Viewed by 13270

Special Issue Editors

Prof. Dr. Maurizio Cutolo

E-Mail Website
Guest Editor
Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Specialties, University of Genova, 16132 Genova, Italy
Interests: systemic sclerosis; rheumatoid arthritis; polymialgia rheumatica; Raynaud’s phenomenon; COVID-19; capillaroscopy; sex hormones; circadian rhythms; glucocorticoids; DMARDs in rheumatoid arthritis; microcirculation; Mediterranean diet; vitamin D; neuroendocrine immunology
Special Issues, Collections and Topics in MDPI journals
Emanuele Gotelli

E-Mail Website
Guest Editor Assistant
Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Specialties, University of Genova, 16132 Genova, Italy
Interests: systemic sclerosis; rheumatoid arthritis; polymyalgia rheumatica; Raynaud’s phenomenon; COVID-19; capillaroscopy; sex hormones; circadian rhythms; glucocorticoids; DMARDs in rheumatoid arthritis; microcirculation; Mediterranean diet; vitamin D; neuroendocrine immunology

Special Issue Information

Dear Colleagues,

Following the first successful Special Issue and continuous new submissions, it is a great pleasure to invite you to contribute to this second Special Issue on the extra-skeletal effects of vitamin D and, in particular, its relationship with the cells and mechanisms involved in immune response. 

In fact, beyond the well-known endocrinological effects on skeletal mineral metabolism, vitamin D, being a steroid hormone, exerts proven antiproliferative and antiviral/antibacterial effects, together with the regulation of the immune system, with an autocrine/paracrine action mechanism. 

The link between hypovitaminosis D and the risk of developing autoimmune diseases has been deeply investigated over the years, with particular interest in infectious and neurological conditions, as well as complex musculoskeletal/connective tissue diseases (rheumatoid arthritis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematosus, etc.). A large plethora of immune cells, such as neutrophils, monocytes/macrophages, and T and B lymphocytes, are characterized by the presence of vitamin D receptor and synthesize the biologically active form of vitamin D, regulating inflammation and innate and adaptive immunity locally and systematically. The COVID-19 pandemic has sparked renewed interest in the anti-inflammatory properties of vitamin D. 

On this basis, the current Special Issue aims to collect the most recent advance concerning immune system modulatory effects exerted by vitamin D, as well as their implications in clinical and therapeutical practice (original articles, reviews, human ex vivo and in vitro translational studies are welcome).

Prof. Dr. Maurizio Cutolo
Guest Editor

Emanuele Gotelli
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vitamin D
  • cholecalciferol
  • calcifediol
  • calcitriol
  • rheumatoid arthritis
  • systemic sclerosis
  • systemic lupus erythematosus
  • type 1 diabetes
  • multiple sclerosis
  • COVID-19
  • innate immunity
  • adaptive immunity
  • monocytes/macrophages
  • T lymphocytes
  • B lymphocytes

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Published Papers (6 papers)

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Editorial

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5 pages, 216 KiB  
Editorial
The 2023’s Growing Evidence Confirming the Relationship between Vitamin D and Autoimmune Diseases
by Maurizio Cutolo and Emanuele Gotelli
Nutrients 2023, 15(22), 4760; https://doi.org/10.3390/nu15224760 - 13 Nov 2023
Cited by 4 | Viewed by 4433
Abstract
The second Special Issue of Nutrients dedicated to “Vitamin D, Immune Response, and Autoimmune Diseases” will include original data and recent achievements from authors who would like to participate in this research topic [...] Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition))

Research

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11 pages, 608 KiB  
Article
Assessing the Impact of Vitamin D Supplementation on Respiratory Infections in Children and Adolescents: A Cross-Sectional Study
by Elena Tanase, Larisa Mihaela Marusca, Florin George Horhat, Monica Susan, Razvan Susan, Razvan Horhat, Stefania Dinu, Tiberiu-Liviu Dragomir and Sonia Tanasescu
Nutrients 2024, 16(22), 3953; https://doi.org/10.3390/nu16223953 - 19 Nov 2024
Viewed by 579
Abstract
Background and Objectives: Recent studies suggest that vitamin D supplementation and higher serum 25-hydroxyvitamin D (25-OHD) concentrations may reduce the incidence of respiratory infections in children and adolescents. This cross-sectional study aimed to evaluate the association between different concentrations of vitamin D supplementation, [...] Read more.
Background and Objectives: Recent studies suggest that vitamin D supplementation and higher serum 25-hydroxyvitamin D (25-OHD) concentrations may reduce the incidence of respiratory infections in children and adolescents. This cross-sectional study aimed to evaluate the association between different concentrations of vitamin D supplementation, serum 25-OHD concentrations, and the frequency of respiratory infections among individuals aged 1 to 18 years, for a duration of 2 years. Methods: Concerning sun exposure in relation to vitamin D, the study took place in Romania, at approximately 45-degree northern latitude. A total of 194 patients were divided into groups based on weekly vitamin D supplementation (<400 IU, 400–800 IU, >800 IU), serum 25-OHD concentrations (<20 ng/mL, 20–30 ng/mL, >30 ng/mL), and age (<6 years, 6–12 years, 12–18 years). The overall incidence of respiratory infections was 41.2%. Results: Participants receiving >800 IU/week had a significantly lower incidence of infections (16.7%) compared to those receiving <400 IU/week (60.0%, p < 0.001). Similarly, participants with serum 25-OHD concentrations >30 ng/mL had an infection rate of 16.7%, compared to 61.4% in those with concentrations <20 ng/mL (p < 0.001). Age-specific analyses revealed that the protective effect of vitamin D was most pronounced in children under 6 years old. Logistic regression showed that higher vitamin D supplementation and serum 25-OHD concentrations were independently associated with reduced odds of respiratory infections (OR = 0.25 and OR = 0.22, respectively, p < 0.001). Conclusions: These findings support the potential role of vitamin D supplementation in preventing respiratory infections in the pediatric population. Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition))
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10 pages, 598 KiB  
Article
Higher Vitamin D Levels before Methotrexate Therapy Initiation Are Associated with Lower Subsequent Mortality in Patients with Rheumatoid Arthritis
by Shahdi K. Malakooti, Hinnah Siddiqui, Brigid Wilson, Taissa Bej, Megan O’Mara, Alexandra Desotelle, Alyssa Lange, Carey L. Shive, Nora G. Singer, Grace A. McComsey, Lenche Kostadinova, Maya Mattar, David A. Zidar and Donald D. Anthony
Nutrients 2024, 16(3), 401; https://doi.org/10.3390/nu16030401 - 30 Jan 2024
Viewed by 1957
Abstract
(1) Vitamin D deficiency is associated with mortality in the general population and has been observed in one rheumatoid arthritis (RA) cohort. Here, we investigate the relationship between 25-hydroxyvitamin D (25(OH)D) levels before methotrexate (MTX) therapy initiation in patients with RA and the [...] Read more.
(1) Vitamin D deficiency is associated with mortality in the general population and has been observed in one rheumatoid arthritis (RA) cohort. Here, we investigate the relationship between 25-hydroxyvitamin D (25(OH)D) levels before methotrexate (MTX) therapy initiation in patients with RA and the subsequent all-cause mortality in a national Veterans Affairs (VA) cohort. (2) This is a retrospective study on RA patients time-oriented around the initial MTX prescription and 25(OH)D levels before starting MTX. We examined survival in patients with 25(OH)D levels > 50 nmol/L and ≤50 nmol/L using the Cox Proportional Hazard Model and fully adjusted for risk factors. (3) In total, 15,109 RA patients were included in the nationwide cohort. RA patients with 25(OH)D levels > 50 nmol/L before starting MTX had a 28% reduced risk of mortality when compared to those with levels ≤ 50 nmol/L (HR: 0.72, CI: 0.64–0.80, p < 0.001) after adjusting for traditional risk factors. (4) In this national RA cohort receiving standard-of-care MTX, patients with 25(OH)D levels > 50 nmol/L have a lower subsequent mortality when compared to those with 25(OH)D levels ≤ 50 nmol/L. It remains to be determined whether increasing Vitamin D levels in RA patients initially found to be Vitamin D deficient impacts their all-cause mortality. Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition))
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12 pages, 1035 KiB  
Article
Vitamin D Supplementation at a Dose of 10 µg/Day in Institutionalized Children with Severe Motor and Intellectual Disabilities
by Yota Sato, Atsushi Kamei, Fumie Endo, Sakura Matsuyama, Hiroyuki Toda and Takeo Kasai
Nutrients 2024, 16(1), 122; https://doi.org/10.3390/nu16010122 - 29 Dec 2023
Cited by 2 | Viewed by 1447
Abstract
Vitamin D (VD) deficiency can lead to health-related consequences. This study determined the effects of VD administration in VD-deficient children with severe motor and intellectual disabilities (SMID). Twenty-eight subjects were included. Among them, 25 subjects with parental consent for VD administration were given [...] Read more.
Vitamin D (VD) deficiency can lead to health-related consequences. This study determined the effects of VD administration in VD-deficient children with severe motor and intellectual disabilities (SMID). Twenty-eight subjects were included. Among them, 25 subjects with parental consent for VD administration were given 10 µg/day (400 IU/day) of VD in April 2021. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured at least 30 days after the start of VD administration. The total VD intake, serum 25(OH)D levels, and ultraviolet (UV) exposure before the blood tests were investigated. The results showed that the median serum 25(OH)D levels were 8.7 ng/mL (4.3–17.2) and 24.0 ng/mL (7.8–39 ng/mL) from March to May in 2020 and 2021, respectively. Among the 25 subjects, 22 with UV exposure had >20 ng/mL serum 25(OH)D level, and 2 without UV exposure had <20 ng/mL serum 25(OH)D level. Three subjects who did not receive VD supplementation had <20 ng/mL serum 25(OH)D level. Taken together, VD supplementation (10 µg/day) is effective in children with SMID in institutional care. Moreover, it may be sufficient for children with UV exposure, but not for those without. Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition))
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17 pages, 11184 KiB  
Article
Age-Dependent Effect of Calcitriol on Mouse Regulatory T and B Lymphocytes
by Agata Śnieżewska, Artur Anisiewicz, Katarzyna Gdesz-Birula, Joanna Wietrzyk and Beata Filip-Psurska
Nutrients 2024, 16(1), 49; https://doi.org/10.3390/nu16010049 - 22 Dec 2023
Viewed by 1429
Abstract
The hormonally active vitamin D3 metabolite, calcitriol, functions as an important modulator of the immune system. We assumed that calcitriol exerts different effects on immune cells and cytokine production, depending on the age of the animal; therefore, we analyzed its effects on [...] Read more.
The hormonally active vitamin D3 metabolite, calcitriol, functions as an important modulator of the immune system. We assumed that calcitriol exerts different effects on immune cells and cytokine production, depending on the age of the animal; therefore, we analyzed its effects on regulatory T lymphocytes and regulatory B lymphocytes in healthy young and old female C57Bl/6/Foxp3GFP mice. In the lymph nodes of young mice, calcitriol decreased the percentage of Tregs, including tTregs and pTregs, and the expression of GITR, CD103, and CD101; however, calcitriol increased the level of IL-35 in adipose tissue. In the case of aged mice, calcitriol decreased the percentages of tTregs and CD19+ cells in lymph nodes and the level of osteopontin in the plasma. Additionally, increases in the levels of IgG and the lowest levels of IFN-γ, IL-10, and IL-35 were observed in the adipose tissue of aged mice. This study showed that calcitriol treatment had different effects, mainly on Treg phenotypes and cytokine secretion, in young and old female mice; it seemed that calcitriol enhanced the immunosuppressive properties of the lymphatic organs and adipose tissue of healthy young mice but not of healthy aged mice, where the opposite effects were observed. Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition))
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Review

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13 pages, 611 KiB  
Review
Vitamin D and Muscle Status in Inflammatory and Autoimmune Rheumatic Diseases: An Update
by Elvis Hysa, Emanuele Gotelli, Rosanna Campitiello, Sabrina Paolino, Carmen Pizzorni, Andrea Casabella, Alberto Sulli, Vanessa Smith and Maurizio Cutolo
Nutrients 2024, 16(14), 2329; https://doi.org/10.3390/nu16142329 - 19 Jul 2024
Viewed by 2500
Abstract
Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of [...] Read more.
Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: “vitamin D, muscle, rheumatic diseases.” Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020–2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold. Full article
(This article belongs to the Special Issue Vitamin D, Immune Response, and Autoimmune Diseases (2nd Edition))
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