Induction of transplantation tolerance by 1,25-dihydroxyvitamin D3

Adorini, Luciano; Penna, Giuseppe; Casorati, Mara; Davalli, Alberto M.; Gregori, Silvia

doi:10.1016/s0041-1345(00)02262-4

Cited by 9 publications

(6 citation statements)

References 11 publications

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“…Therefore, VitD3 could become a suitable immunomodulating drug for application to Th1‐type immune diseases such as psoriasis, multiple sclerosis and graft versus host disease. ( 30–32 )…”

Section: Discussionmentioning

confidence: 99%

1α,25‐Dihydroxyvitamin D3 downmodulates the functional differentiation of Th1 cytokine‐conditioned bone marrow‐derived dendritic cells beneficial for cytotoxic T lymphocyte generation

et al. 2006

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D endritic cells play a critical role in both innate and adaptive immunity by producing chemokines and cytokines, and by presenting antigens to antigen-specific T cells.(1,2) Recently, it has been demonstrated that there are functionally different DC subsets. We have reported that a BMDC subset generated from BM cells under Th1-biasing conditions (BMDC1, induced by GM-CSF, IL-3, IL-12 and IFN-γ) enhances type 1 immunity to a greater extent than a BMDC subset generated under neutral conditions (BMDC0, induced by GM-CSF and IL-3).(3) CD8 + T cells stimulated with allogeneic BMDC1 showed much higher IFN-γ production and cytotoxic activity than T cells co-cultured with BMDC0. In addition, vaccination of tumor-bearing mice with tumor antigen-pulsed BMDC1 strongly enhanced therapeutic effect by tumor-antigen-specific Th1 cells.(4) Moreover, it has also been reported that regulatory DC subset can be induced from mouse BM cells in the presence of suppressive drugs such as IL-10 and TGF-β.(5-7) From these findings, it is speculated that heterogeneous DC subsets with quite different functions are generated from BM precursor cells under different culture conditions. Therefore, it is of great importance to investigate the effect of immunomodulating drugs on functional differentiation of BMDC subsets.1α,25-Dihydroxyvitamin D3 (the active form of vitamin D3) is a well-known pro-hormone-like vitamin, and is involved in calcium metabolism. Recent investigations have demonstrated that VitD3 has a potent immunomodulating function.(8) Namely, mice fed or treated with VitD3 showed low occurrence and severity of experimental autoimmune encephalomyelitis, which is a Th1-dependent autoimmune disease.(9) Moreover, naïve T cells that are treated with VitD3 alone or a combination of VitD3 and dexamethasone differentiate into IL-10-producing T cells in vitro. (10,11) In addition, VitD3 influences the differentiation and functions of DC.(12-15) Thus, VitD3 is considered as one of the important immunomodulating drugs that inhibit Th1-dependent immune responses through regulating the function of DC and T cells. Some molecular mechanisms for inhibition of type 1 immunity by VitD3 have been reported. (16,17) However, though it has been shown that VitD3 suppresses the production of Th1 cytokines, it is not yet known whether VitD3 modulates the effect of Th1 cytokines on immune cells. Thus,

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Section: Discussionmentioning

confidence: 99%

1α,25‐Dihydroxyvitamin D3 downmodulates the functional differentiation of Th1 cytokine‐conditioned bone marrow‐derived dendritic cells beneficial for cytotoxic T lymphocyte generation

et al. 2006

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“…1 α ,25‐dihydroxyvitamin D 3 [(1 α ,25(OH) 2 D 3 ], the active metabolite of vitamin D 3, is a liphophilic steroid hormone which exerts its actions through binding to a nuclear receptor, the vitamin D receptor (nVDR) [1]. Traditionally 1 α ,25(OH) 2 D 3 has been associated with calcium homeostasis but the discovery of the nVDR in most cells of the immune system such as monocytes, macrophages, dendritic cells [2], T and B lymphocytes [3–7] suggested a role of the hormone in the immune system. Indeed, 1 α ,25(OH) 2 D 3 stimulates the differentiation and maturation of monocytes [8] while it inhibits the differentiation and maturation of dendritic cells [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, 1 α ,25(OH) 2 D 3 stimulates the differentiation and maturation of monocytes [8] while it inhibits the differentiation and maturation of dendritic cells [9,10]. The steroid hormone also diminishes T cell proliferation [11,12] as well as production of cytokines required for Th1 differentiation such as interleukin (IL)‐12 [2,13], interferon (IFN)‐ γ [14], IL‐2 [15,16] as well as granulocyte‐macrophage colony stimulating factor (GM‐CSF) [17]. On the other hand, 1 α ,25(OH) 2 D 3 is able to enhance the production of Th2‐cytokines such as IL‐4 and IL‐10 [2,18–20] as well as of the Th3‐cytokine transforming growth factor (TGF)‐ β [21,22].…”

Section: Introductionmentioning

confidence: 99%

1α, 25-dihydroxyvitamin D3 increases IgA serum antibody responses and IgA antibody-secreting cell numbers in the Peyer's patches of pigs after intramuscular immunization

Stede

Verfaillie

Cox

et al. 2004

Clinical and Experimental Immunology

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SUMMARY Pigs were injected intramuscularly (i.m.) twice with human serum albumin (HSA) with or without 1α,25‐dihydroxyvitamin D3[1α,25(OH)2D3] with a 5‐week interval. The supplementation of 1α,25(OH)2D3 enhanced the HSA‐specific IgA serum antibody response but decreased the IgM, IgG, IgG1 and IgG2 responses. Furthermore, higher numbers of HSA‐specific IgA antibody‐secreting cells were obtained in systemic lymphoid tissues (local draining lymph node, spleen and bone marrow) as well as in Peyer's patches and lamina propria of the gut (GALT). In addition, the in vivo mRNA expression for Th1 [interferon (IFN)‐γ, interleukin (IL‐2)], Th2 (IL‐4, IL‐6 and IL‐10) and Th3 [transforming growth factor (TGF)‐β] cytokines as well as the percentage of different cell subsets (CD2+, CD4+, CD8+, IgM+, MHC II+, CD25+) of monomorphonuclear cells from the local draining lymph node were determined at different time‐points after the i.m. immunizations. Cytokine profiles did not resemble a typical Th‐cytokine profile using 1α,25(OH)2D3: higher levels of IL‐10 and significantly lower levels of IL‐2 were observed the first day after the primary immunization. However, significantly higher levels of IL‐2 and significantly lower levels of IFN‐γ were observed the first day after the second immunization. Furthermore, after the second immunization TGF‐β mRNA expression decreased more quickly in the 1α,25(OH)2D3 group. This difference became significant 7 days after the second immunization. One week later a significantly higher percentage of CD25+ cells was observed in this group, indicating more activated T and B cells using the steroid hormone. These results suggest that in pigs the addition of 1α,25(OH)2D3 to an intramuscularly injected antigen can enhance the antigen‐specific IgA‐response and prime GALT tissues, but the relation with cytokines and cell phenotype in the local draining lymph node needs further clarification.

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“…The production of 1,25(OH) 2 D 3 increases throughout the maturation of dendritic cells (DCs) due to a higher expression of CYP27B1 (8). However, 1,25(OH) 2 D 3 keeps DCs in an immature state to preserve immune tolerance (43,55,56). From the DCs perspective, 1,25(OH) 2 D 3 hampers interaction and priming of T cells inhibiting expression of receptors CD40, CD80, and CD86 in the DCs' surface (55,56), diminishing the secretion of IL-12 and concurrently of IFN-γ (19,33,(55)(56)(57), and suppressing DCs' migration to lymph nodes due to reduction of CCL21 and its receptor CCR7, blunting antigen presentation to T-cells (43,44).…”

Section: Innate Immunitymentioning

confidence: 99%

Insights Into the Role of Vitamin D as a Biomarker in Stem Cell Transplantation

et al. 2020

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Vitamin D was discovered 100 years ago and since then multiple studies have consistently proved its effect on bone health and mineral metabolism. Further research has also explored its so-called "non-classical" biological effects, encompassing immune regulation and control of cell proliferation and differentiation. Vitamin D downregulates pro-inflammatory immune cells and subsequently their cytokine production, while enhancing the anti-inflammatory subsets, thus mediating inflammation and fostering a more tolerogenic environment. Its biological action is exerted through the vitamin D receptor, a nuclear receptor that mediates gene transcription and is expressed in most cells from the innate and adaptive immunity. Owing to its immune-modulatory properties, its role in cancer pathophysiology, hematology disorders and stem cell transplantation has also been investigated. Vitamin D deficiency causes immune imbalance and cytokine dysregulation, contributing to some autoimmune diseases. In the hematopoietic stem cell transplant setting this could lead to complications such as acute and chronic graft-versus-host disease, ultimately impacting transplant outcomes. Other factors have also been linked to this, including specific polymorphisms of the vitamin D receptor in both stem cell donors and recipients. Nevertheless, studies thus far have shown conflicting results and the use of vitamin D or its receptor as biomarkers has not been validated yet, therefore there are no evidence-based consensus guidelines to guide clinicians in their day-today practice. To gain more insight in this topic, we have reviewed the existent literature and gathered the current evidence. This is an overview of the role of serum vitamin D and its receptor as biomarkers for clinical outcomes in patients undergoing hematopoietic stem cell transplantation. Further prospective studies with larger cohorts are warranted to validate the viability of using serum vitamin D, and its receptor, as biomarkers in potential stem cell donors and patients, to identify those at risk of post-transplant complications and enable early therapeutic interventions.

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Induction of transplantation tolerance by 1,25-dihydroxyvitamin D3

Cited by 9 publications

References 11 publications

1α,25‐Dihydroxyvitamin D3 downmodulates the functional differentiation of Th1 cytokine‐conditioned bone marrow‐derived dendritic cells beneficial for cytotoxic T lymphocyte generation

1α,25‐Dihydroxyvitamin D3 downmodulates the functional differentiation of Th1 cytokine‐conditioned bone marrow‐derived dendritic cells beneficial for cytotoxic T lymphocyte generation

1α, 25-dihydroxyvitamin D3 increases IgA serum antibody responses and IgA antibody-secreting cell numbers in the Peyer's patches of pigs after intramuscular immunization

Insights Into the Role of Vitamin D as a Biomarker in Stem Cell Transplantation

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