Synergistic Effects of Interferon-γ and Vitamin D3 Signaling in Induction of ILT-3highPDL-1high Tolerogenic Dendritic Cells

Švajger, Urban; Rožman, Primož

doi:10.3389/fimmu.2019.02627

Cited by 21 publications

(22 citation statements)

References 43 publications

(47 reference statements)

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“…The active state of Vit D and IFN-γ are both pleiotropic endogenous immune modulators and may be useful in immunogenicity and immune tolerance. 23…”

Section: Discussionmentioning

confidence: 99%

“…The active state of Vit D and IFN-c are both pleiotropic endogenous immune modulators and may be useful in immunogenicity and immune tolerance. 23 Vit D prevents the development of autoantibody and reduces the number as well as the action of dendritic cell-related pathways, thus it causes suppression of T cell activation. Active vitamin D;1,25(OH)D has additional immunomodulatory activities, it prevents the proliferation of B cells before possessing the capacity to secrete immunoglobulin.…”

Section: Discussionmentioning

confidence: 99%

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Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus

Abo-Shanab

Kholoussi

Kandil

et al. 2020

Lupus

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Background Juvenile onset systemic lupus erythematosus JO-SLE patients usually exhibit a more aggressive disease course compared to adult patients. Vitamin D deficiency is proposed to be associated with increased disease activity and flares of numerous autoimmune diseases like SLE, rheumatoid arthritis, and scleroderma. Objective To evaluate the level of IL-17, IFN-γ, and 25-OH Vit D in JO-SLE patients versus healthy controls, and determine the correlation of those inflammatory mediators with SLE disease activity and damage scores. Furthermore, to analyze the relationship between 25-OH Vit D levels with the inflammatory cytokines (IFN-γ and IL-17) in JO-SLE patients. Patients and methods Fifty JO-SLE patients and 25 controls were included in this study. Clinical and laboratory data of patients at the time of the study were recorded. SLE disease activity and damage were assessed using the SLEDAI-2K disease score and SLICC damage index, respectively. Plasma 25-OH Vit D, IFN-γ, and IL-17 concentrations were determined using the human ELISA kit. Results Plasma 25-OH Vit D levels (20 ng/mL) were significantly lower in JO-SLE patients compared to (31 ng/mL) controls (P = 0.014). Plasma levels of IFN-γ and IL-17 were significantly higher (163.5 and 25.5 pg./mL) in JO-SLE patients than (68.3 and 3 pg./mL) that of controls (P = 0.016 and P = 0.013). There was a significant negative correlation between 25-OH Vit D levels and SLEDAI-2K (R= -0.431) as well as IFN-γ (R= -0.471) plasma level (P = 0.022 and P = 0.027). Conclusion IFN-γ and IL-17 were significantly higher in JO-SLE patients, while 25-OH Vit D was significantly lower compared to controls. There was a negative correlation between 25-OH Vit D and each of SLEDAI-2K and IFN-γ.

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“…The active state of Vit D and IFN-γ are both pleiotropic endogenous immune modulators and may be useful in immunogenicity and immune tolerance. 23…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus

Abo-Shanab

Kholoussi

Kandil

et al. 2020

Lupus

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“…However, not all inhibitory factors expressed by a DCreg necessarily contribute to the cell’s regulatory activities. Thus, vitamin D/IFNγ-induced human DCreg express IL-10, HLA-G, PD-L1 and low levels of FasL, but among these it was only their expression of PD-L1 that was reported as integral to the cell’s regulatory activities ( 60 ). It is also apparent that inhibitory receptors can play more than one role in immune tolerance.…”

Section: Introductionmentioning

confidence: 99%

Regulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease

2021

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Dendritic cells (DC) are antigen-presenting cells that can communicate with T cells both directly and indirectly, regulating our adaptive immune responses against environmental and self-antigens. Under some microenvironmental conditions DC develop into anti-inflammatory cells which can induce immunologic tolerance. A substantial body of literature has confirmed that in such settings regulatory DC (DCreg) induce T cell tolerance by suppression of effector T cells as well as by induction of regulatory T cells (Treg). Many in vitro studies have been undertaken with human DCreg which, as a surrogate marker of antigen-specific tolerogenic potential, only poorly activate allogeneic T cell responses. Fewer studies have addressed the abilities of, or mechanisms by which these human DCreg suppress autologous effector T cell responses and induce infectious tolerance-promoting Treg responses. Moreover, the agents and properties that render DC as tolerogenic are many and varied, as are the cells’ relative regulatory activities and mechanisms of action. Herein we review the most current human and, where gaps exist, murine DCreg literature that addresses the cellular and molecular biology of these cells. We also address the clinical relevance of human DCreg, highlighting the outcomes of pre-clinical mouse and non-human primate studies and early phase clinical trials that have been undertaken, as well as the impact of innate immune receptors and symbiotic microbial signaling on the immunobiology of DCreg.

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“…This inhibitory effect was occurred with the enhanced expression of CTLA-4, PD1 or PD-L1 on regulatory cells in the immune system, and also with the suppressive effect of IL-10, which is produced by Treg cells (28,29). Additionally, IFN- can synergistically enhance the suppression in proliferative responses with vitamin D3 by expressions of immunoglobulin-like transcript (ILT)-3 and programmed death ligand (PDL)-1 on tolerogenic DCs (30). In the present study, we observed reduced number of IFN- secreting Th lymphocytes in both drug-naïve and pSS treated patients, while the reduction was striking in drug-naïve patients.…”

Section: Discussionmentioning

confidence: 99%

1,25-dihydroxyvitamin D3 regulates t helper and b lymphocyte responses substantially in drug-naive primary Sjögren’s syndrome patients’ mononuclear cells

et al. 2021

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Objectives: A correlation between vitamin D deficiency and primary Sjögren's Syndrome (pSS) has already been described. The limited data have been reported regarding the pathological relevance of vitamin D in primary Sjögren's syndrome. In this study, the peripheral blood mononuclear cells were cocultured with 1,25-dihydroxyvitaminD3 to determine the modulatory effect of vitamin D3 on T and B lymphocyte phenotypes in pSS.Method: Venous blood samples were collected from 11 in treatment phase and 9 drug-naive pSS patients. Peripheral blood mononuclear cells (PBMC) were isolated and separately cultured in the presence and absence of 1,25-dihydroxyvitaminD3 (10mM) for 5 days of culture period. Lymphocyte proliferation was analyzed for CFSE signaling via flow cytometry. CD3+CD4+ cells were analyzed for intracellular IFN- and IL-17 expressions. CD19+IgD cells were analyzed for CD38 and CD27 expressions to evaluate naïve and memory B cell subsets. Culture supernatants were analyzed for the IFN-, IL-17 and IL-10 cytokine secretions via flow cytometry.Results: 1,25-dihydroxyvitaminD3 significantly decreased Th lymphocyte proliferative responses in drug-naïve (p<0.005) and treated pSS patients (p<0.05), and B lymphocyte proliferation in drug-naïve pSS PBMC cultures (p<0.01) compared to mononuclear cell cultures alone. 1,25-dihydroxyvitamin D3 significantly decreased IFN- and IL-17 secreting Th cells in both drug naïve (p<0.005 and p<0.01, respectively) and treated subjects (p<0.05 and p<0.05, respectively) by increasing FoxP3 expressing CD4+CD25+ Treg cell frequency. Plasma B lymphocytes significantly reduced in the presence of 1,25-dihydroxyvitaminD3 in drug naïve pSS (p<0.001) and treated patients (p<0.05) mononuclear cell cultures compared to PBMC cultures alone. Total memory B cell subsets significantly increased with 1,25-dihydroxyvitaminD3 in drug naïve pSS when compared with PBMC cultures alone (p<0.005). IFN- and IL-17 cytokine levels in culture supernatants significantly reduced (p<0.05 and p<0.01, respectively) in drug naïve pSS patients' PBMC cultures with 1,25-dihydroxyvitaminD3, and IL-10 levels significantly enhanced in both drug-naïve (p<0.01) and treated pSS patients' PBMC cultures (p<0.01) in the presence of 1,25-dihydroxyvitaminD3. Conclusion:In conclusion, 1,25-dihydroxyvitaminD3 regulated immune responses in both treated and drug-naïve pSS patients, but have a more pronounced modulatory effect on mononuclear cell responses in drug-naive pSS patients.

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Synergistic Effects of Interferon-γ and Vitamin D3 Signaling in Induction of ILT-3highPDL-1high Tolerogenic Dendritic Cells

Cited by 21 publications

References 43 publications

Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus

Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus

Regulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease

1,25-dihydroxyvitamin D3 regulates t helper and b lymphocyte responses substantially in drug-naive primary Sjögren’s syndrome patients’ mononuclear cells

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