Tregs for the Rest of Us: Part 2 Vitamin A & D

Both Vit A and D are involved in the regulation of the immune system and inflammation of tissue. In order to be used by the body, they need to be modified by enzymes.

There are many different kinds of Tregs. for simplicity, I have not specified the types in this review.

Vit A Derivatives and Treg Function

For reference, a derivative is an analogous compound to the vitamin. A metabolite is a compound created in vivo. When I say Vit A (or D3) given to a patient, I am referring to derivatives. I specifically note when I am discussing metabolites.

Vit A can be a problem unless there is the proper level; both too much and too little is problematic.. A deficiency can cause a Treg imbalance (too much Th1 and not enough Th2). A different study showed that too much Vit A in vitro causes development of Th2 cells.

A metabolite of Vit A (ATRA) converts one type of T-cells into Treg cells (again, in vitro). The resulting Treg cells suppressed effector Tcells, particularly in intestinal epithelial cells.  ATRA is also able to prevent the conversion of Treg cells into inflammatory TH17 cells. This provided some protection in a colitis model. There is some evidence that probiotic bacteria and Omega-3 fatty acids affects the functioning of ATRA in the body.

Vitamin D3 Derivatives and Treg Function

UVB exposure as well as a topical Vit D3 treatment can lead to creation of Tregs on the skin. Supplementation has also shown to have a positive effect with brain inflammation and diabetes (in terms of increasing Tregs).

MS patients have lower levels of Vit D3 metabolites, suggesting that the Vit D3 metabolites have a role in controlling inflammation and Treg formation. There is a possibility as well that Vit D3 metabolites affect the stability of Tregs in diabetic patients, but more studies are need to clarify any role they have.

Vit A and Vit D Crosstalk to Maintain Immune Homeostasis

Vit Aand  Vit D's signaling receptors are interconnected. There are two cell signaling pathways which are the same for Vit A and D. These pathways use different macromolecules to signal for either Vit D or Vit A. This leads to the hypothesis that they are both involved in maintaining a healthy balance in the immune system.

My Thoughts

Although it is not uncommon to have Vit D levels checked in a person with allergies, I have not done so for James. We live in an area with a lot of sun and he is outside without sunscreen each day. I have not heard of people testing Vit A levels, although they might. He is offered (but doesn't always eat) a wide variety of fruits and vegetables. I do not give him a multivitamin.

Since too little Vit A skews to too much much Th1 and not enough Th2, one might think that a deficiency would be good for those with allergies. However, I, personally, would not withhold a vitamin in the hopes that it changes the immune system. Vitamins have other functions besides affecting the immune system and if you over-activate the Th1 arm, there are also serious consequences (pot meet fire).

If his levels are low, I would suspect an underlying issue (he can't process Vit D for some reason, not that he doesn't get enough). It is another thing that I may address when he is done with treatment.

Part One