Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort

Marinho, António; Carvalho, Cláudia; Boleixa, Daniela; Bettencourt, Andreia; Leal, Bárbara; Guimarães, Judite; Neves, Esmeralda; Oliveira, José Carlos; Almeida, Isabel; Farinha, Fátima; Costa, Paulo; Vasconcelos, Carlos; Silva, Ana Martins

doi:10.1007/s12026-016-8829-3

Cited by 38 publications

(27 citation statements)

References 47 publications

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“…Indeed, sustained high levels of TNF-α, IL-6 and IFN-γ are associated with increased disease severity during pneumococcal pneumonia [33]. The ability of 1,25(OH) 2 D 3 to control inflammation through IL-10 is intriguing, and is consistent with its reported anti-inflammatory effects [34,35,36,37,38] and ability to induce functional regulatory T cells (Treg) [39,40]. Our data suggest this may be due to an increased CD14 expression although our small sample size limit the significance of this finding.…”

Section: Discussionmentioning

confidence: 86%

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

et al. 2016

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Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.

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Section: Discussionmentioning

confidence: 86%

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

et al. 2016

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“…Thus, it might be logical to move forward with Treg cell therapy trials (in lupus) that use a concomitant IL‐2 therapy to maximize the effects of individual therapies. In addition, vitamin D supplementation may augment the potential efficacy of adoptive Treg cell therapy, as this treatment has been shown to increase FoxP3/IL‐17A in SLE patients . Finally, it should be noted that it is unlikely that the rapid reduction in adoptively transferred Treg cell numbers in the blood was due to a dramatic change in cell surface phenotype, including loss of CD25 or increased CD127 expression.…”

Section: Discussionmentioning

confidence: 99%

Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus

Dall’Era

Pauli

Remedios

et al. 2019

Arthritis & Rheumatology

130

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Objective Adoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease. Methods We describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment. Results Deuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon‐γ pathway and a reciprocal augmentation of the interleukin‐17 (IL‐17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL‐17 production. Conclusion We report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses.

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“…2 ). Recent evidences have shown the potential benefit of vitamin D supplementation in SLE patients (Table 1 ) [ 52 , 62 , 86 – 88 ]. Tabasi et al [ 89 ] isolated peripheral blood mononuclear cells (PBMCs) from 25 SLE patients and cultured them in the presence of 50 nM of 1,25(OH)2D3.…”

Section: Role Of Vitamin D Supplementation In Sle Improvementmentioning

confidence: 99%

Role of vitamin D deficiency in systemic lupus erythematosus incidence and aggravation

Hassanalilou

Khalili

Ghavamzadeh

et al. 2017

Autoimmun Highlights

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Vitamin D is one of the main groups of sterols; playing an important role in phospho-calcic metabolism. The conversion of 7-dehydrocholesterol to pre- vitamin D3 in the skin, through solar ultraviolet B radiation, is the main source of vitamin D. Since lupus patients are usually photosensitive, the risk of developing vitamin D deficiency in is high in this population. Although evidences showed the connotation between systemic lupus erythematosus (SLE) and vitamin D through which SLE can lead to lower vitamin D levels, it is also important to consider the possibility that vitamin D deficiency may have a causative role in SLE etiology. This paper analyzes existing data from various studies to highlight the role of vitamin D deficiency in SLE occurrence and aggravation and the probable efficacy of vitamin D supplementation on SLE patients. We searched “Science Direct” and “Pub Med” using “Vitamin D” and “SLE” for finding the studies focusing on the association between vitamin D deficiency and SLE incidence and consequences. Evidences show that vitamin D plays an important role in the pathogenesis and progression of SLE and vitamin D supplementation seems to ameliorate inflammatory and hemostatic markers; so, can improve clinical subsequent.

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Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort

Cited by 38 publications

References 47 publications

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus

Role of vitamin D deficiency in systemic lupus erythematosus incidence and aggravation

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