Vitamin D controls T cell antigen receptor signaling and activation of human T cells

Essen, Marina Rode von; Kongsbak, Martin; Schjerling, Peter; Ølgaard, Klaus; Ødum, Niels; Geisler, Carsten

doi:10.1038/ni.1851

Cited by 480 publications

(400 citation statements)

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“…[16] Decreasing vitamin D 3 levels over recent decades has decreased immune effectiveness [99][100][101] fueling HPV persistence, which apparently contributes toward increasing the incidence of many cancers. Our results provide worldwide evidence that estrogen and old age (via ROS), rather than industrialized chemical pollutants, plays major roles in most cancers and suggests there may be even more HPV-related cancers than previously thought.…”

Section: Discussionmentioning

confidence: 99%

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

Godar

Gurov²,

Merrill

2017

JER

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Because we observed increasing incidences over time, advancing age, higher estrogen levels, decreasing UVB (290-315 nm) doses, or lower vitamin D3, and Human Papillomavirus hiding in immune-privileged sites of hair follicles play roles in melanoma, we wondered if the majority of cancers might have similar carcinogenic drivers. To investigate this possibility, we performed worldwide analysis of all sites but skin cancer over time , advancing age, and UVB doses for males and females with all skin types and ages (0-85+) and in five age groups using IARC data. To investigate Human Papillomavirus's role, we analyzed the incidences of breast, prostate, and colon cancers in a developed country with European ancestry (New Zealand) having high amounts of androgenic hair and a developing country with Asian ancestry (India) having low amounts of androgenic hair. To potentially add epidemiology to the already established role of estrogen in cancer, we analyzed males and females in various countries around the world using the incidence of breast cancer (> 70 yr.) as an established indicator of estrogen levels. The analysis reveals cancer incidences are steadily increasing over time in developed but not developing countries regardless of skin type. Only US white, but not black, breast, prostate, and colon cancer incidences in the oldest age group significantly decreased with increasing UVB dose suggesting a role for vitamin D3. The data suggests the carcinogenic drivers in many cancers are estrogen, increasing age (or reactive oxygen species), decreasing vitamin D3 levels, and persistence of Human Papillomavirus infection in immune-privileged sites.

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Section: Discussionmentioning

confidence: 99%

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

Godar

Gurov²,

Merrill

2017

JER

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“…Vitamin D receptor is found in significant concentrations in the lymphocyte T and macrophages populations, but the highest concentration is observed in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. This suggests that phagocytes may communicate with T and B cells through calcitriol [20,21]. When vitamin D is present, it blocks the features of the adaptive immune system that would lead to autoimmunity.…”

Section: The Role Of Vitamin D In the Immune System-lymphocytes T And Bmentioning

confidence: 99%

“…When vitamin D is present, it blocks the features of the adaptive immune system that would lead to autoimmunity. Animal studies show that when calcitriol is absent, the cells of the immune system are more likely to attack the healthy cells of the body (autoimmunity) [20]. There are two ways that vitamin D influences the immunity.…”

Section: The Role Of Vitamin D In the Immune System-lymphocytes T And Bmentioning

confidence: 99%

“…Blocking the production of these cells results in diminished ability of T cells to recognize the native protein as foreign. This leads to decrease in killer T cells production [20][21][22]. In other words, the presence of adequate levels of vitamin D and calcitriol keeps the T cells from attacking the body's own tissues.…”

Section: The Role Of Vitamin D In the Immune System-lymphocytes T And Bmentioning

confidence: 99%

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Immunomodulatory Effect of Vitamin D in Children with Allergic Diseases

Stelmach¹,

Jerzyńska²,

Podlecka³

2017

A Critical Evaluation of Vitamin D - Basic Overview

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The discovery that many cells express vitamin D receptors and the recognition of widespread vitamin D insufficiency has stimulated interest in the potential role of vitamin D in nonskeleton conditions. There is an increasing evidence to support the role of vitamin D pathway in the regulation of the function of both innate and adoptive immune systems. Vitamin D regulates immune function by inhibiting the differentiation and maturation of human dendritic cells, enhancing interleukin (IL)-10 and tumor growth factor-β (TGF-β) secretion and inhibiting T-cell functions. Vitamin D has the ability to suppress inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interferon gamma (IFN-γ), and interleukin-2 (IL-2), while it increases the generation of anti-inflammatory cytokines IL-4 and IL-10. In B cells, vitamin D3 has also been shown to suppress immunoglobulin E (IgE) antibody class switch partly through the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

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“…It has been established that phospholipase Cγ1 induction depends on vitamin D and receptor thereof. Naïve T lymphocytes do not express VDR; however, initiation of the T cell receptor signaling pathway via an alternative route (mitogen-activated protein kinase p38) leads to induction VDR and phospholipase Cγ1 required for the subsequent successful launch of the classic T cell signal and activation of T lymphocytes [33]. In whole, impact of calcitriol on the immune system includes modulation of the T cell receptor, reduction in Th1/Th17 CD4(+) T lymphocytes, increase in regulatory T lymphocytes, suppression of the T lymphocyte-mediated immunoglobulin (Ig) G synthesis and worsening of differentiation of dendritic cells.…”

mentioning

confidence: 99%