Vitamin D & the dermis: Sunlight may be needed to prime T cells to function in skin

[Ezliving_Jim]

Vitamin D & the dermis

Sunlight may be needed to prime T cells to function in skin

May 1, 2007 By: Bob Roehr Dermatology Times Stanford, Calif.—Vitamin D can be completely synthesized into its active form in the skin,without the involvement of the liver and kidneys,and this process is important to priming T cells towork in the skin,a California researcher says.

The new study by Hekla Sigmundsdottir, Ph.D., a postdoctoral researcher at the Stanford University School of Medicine, also suggests that skin must be exposed to sufficient UVB light to generate adequate programming of T cells to function in the dermis.

Dr. Sigmundsdottir has provided several pieces of an emerging new picture of vitamin D that differs significantly from what was known just a few years ago. The new model places all aspects of formation of the vitamin and its hydroxylation into the active form of 1,25(OH)2 D3 in the skin, and identifies a new and important role for 1,25(OH)2 D3 in immune function.

The classic model posited that an inactivated form of vitamin D is generated in the upper layers of the skin through exposure to UVB radiation. The molecule would then travel a convoluted pathway to the liver and kidneys, where it was hydroxylated into the active form before migrating to other tissue, including the skin, for use by the body.

Dr. Sigmundsdottir has found that dendritic cells can metabolize vitamin D into the active form 1,25(OH)2 D3. Moreover, 1,25(OH)2 D3 provides a mechanism for local cutaneous "imprinting" of responding T cells so that they generate an immune response specific to the microenvironment of the skin.

Using microarray analysis and other techniques, she determined that the genes that are sufficient to hydroxylate vitamin D into its active form are present in dendritic cells and T cells. In culture, only dendritic cells completely expressed the genes that enabled them to fully process vitamin D through both stages of hydroxylation. The last step of that process was present when T cells were co-cultured with dendritic cells.

Parallel research in other labs also recently has demonstrated the capacity of skin cells to produce the completely activated form of vitamin D.

Immune response

Teasing out the effect of this on immune function required even more complicated research.

Naive T cells do not express the CCR10 receptor, a key receptor that allows them to respond to the skin-specific chemokine CCL27, secreted by keratinocytes, Dr. Sigmundsdottir tells Dermatology Times. But 1,25(OH)2 D3 induces T cells to express the CCR10 receptor.

Her work used several assays, including chemotaxis assays, to show that concentrations of 1,25(OH)2 D3 found in normal serum were insufficient for effective upregulation of CCR10, nor did other compounds such as retinoic acid cause such upregulation. But the generation of 1,25(OH)2 D3 by dendritic cells increased concentration of the molecule in the microenvironment sufficiently to cause that upregulation. The effect was greater with CD8+ cells than with CD4+ cells.

She also determined that 1,25(OH)2 D3 only upregulated CCR10.
"It did not increase the expression of other receptors, such as CCR4, that can mediate T-cell recruitment from blood into the dermis. It also had no effect on receptors used to traffic T cells to lymph nodes, while it inhibited upregulation of receptors that would guide the cells to the gut."

Sunlight triggers

The findings suggest that sunlight-generated vitamin D3 may act mainly on T cells in the skin itself, after the T cells have infiltrated the dermis from the blood, inducing CCR10 to "program" T-cell attraction and retention in the epidermis.

This suggests to Dr. Sigmundsdottir the importance of exposing skin to sufficient UVB light to generate adequate programming of T cells. She acknowledges that the issue is controversial with many dermatologists and notes that such exposure does not have to be lengthy.

She also sees limitations to supplementation. While both sunlight-induced vitamin D3 and the dietary form D2 need to be hydroxylated, in her experiments, the dietary form was not as effective at inducing the attraction of T cells to the upper layers of the skin.

Dr. Sigmundsdottir says, "It is possible that the dietary form of vitamin D may not be efficient enough to generate sufficiently strong immune responses in the skin."

For more information:

Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007 Mar;8(3):285-293. Epub 2007 Jan 28.



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[solarmeter®]

This is over my head. Where's the mW/cm²? I understand those.

[Ezliving_Jim]

Long story short; natural vitamin D3 processed with UV light is necessary for healthy T cell immune function and is much more effective than vitamin D2 supplements.

[Editor-in-Chief]

Sunshine Can Actually Be Good For You


New Stanford Research

HEALTH
Link to ABCNewsVideo: http://abclocal.go.com/kgo/story?sec...lth&id=5347278

May 28 - KGO - There's more fuel for the debate over the risk of skin cancer versus the benefits of Vitamin D produced in our skin by sunlight. New research out of Stanford shows getting Vitamin D from the sun might actually help the skin protect itself.

We know sunlight exposure causes our skin cells to produce Vitamin D. Now Stanford University pathology researchers have discovered that it can trigger a protective immune response in the skin itself. Hekla Sigmundsdottir and her colleagues studied immune system cells called T-cells. They found that Vitamin D produced by sunlight causes these protective cells to travel to the skin.

Hekla Sigmundsdottir, Ph.D., Stanford Post-Doctoral Pathology Researcher: "I think just the fact that the Vitamin D can attract or draw T-cells towards the skin is a function that is needed. I think that's why we make vitamin in the skin."

Milk and other dairy can also be a source of Vitamin D. So the researchers tested this type of Vitamin D as well. What they found was that beneficial effects were far less pronounced.

Hekla Sigmundsdottir: "Vitamin D that we obtain through the diet seems to be less effective than the vitamin that is generated in the sun."

As they wrote in the journal, Nature Immunology, the finding suggests our skin has evolved a clever trick to protect itself from sunlight.

Hekla Sigmundsdottir: "I think a little sunshine is good for you. I think the reason we make Vitamin D in the skin indicates that it's there for a reason."

In fact, other research shows small amounts of sun may actually reduce the risk of breast and prostate cancer. But sun worshippers beware -- Dr. Sigmundsdottir means it when she says a little because too much sun is still bad for you.

It only takes 10 to 15 minutes of sun exposure, a couple times a week, to make enough Vitamin D. More sunlight than that doesn't help, and can increase your risk of skin cancer.

To learn more about the health benefits of sunlight, click here.
Copyright 2007, ABC7/KGO-TV/DT.


Sidebar:

For more information, contact:
Hekla Sigmundsdottir, PhD
Post-Doctoral Scholar
Department of Pathology
154B Pathology, Building 102
Eugene Butcher
Stanford, California 94305
Or visit: www.sciencentral.com