There is much debate regarding the ideal way to categorize vitamin D. It does not fit the classic definition of a vitamin. Some call it a pre-hormone, while others argue it’s a prohormone. Regardless, one thing is clear: Once activated in the body, vitamin D behaves as a steroid hormone. This means it has the power to turn genes on and off, affecting cells in the body throughout their life cycle.
The effect of long-term vitamin D deficiency
But what happens when vitamin D levels become too low? Although in most cases, individuals don’t develop symptoms of deficiency, this can lead to chemical processes becoming altered in the body, most commonly leading to increased inflammation and altered immune function. Now, what happens when an individual is immunocompromised to begin with? Research suggests that in many cases, this may lead to increased disease activity and symptom severity.
Vitamin D & lupus overview
Let’s take systemic lupus erythematosus (SLE) as a example. SLE is an autoimmune disease that occurs when the body’s immune system mistakes its own healthy tissue for foreign invaders and begins to attack itself. This results in inflammation of the affected tissues or organs. Lupus can act on every system in the body. However, this disease more commonly affects the skin, joints and kidneys.
The two main components of lupus also happen to be two important systems regulated by vitamin D: the immune system and inflammatory response. Therefore, it comes as no surprise that an abundance of research has produced positive findings regarding the relationship between vitamin D and lupus. In fact, research has found that vitamin D deficiency is associated with increased disease activity among both children and adults with lupus. In addition, vitamin D supplementation helps decrease disease activity, thus improving symptom severity.
Researchers theorize that the mechanism behind vitamin D’s role in immunity among lupus patients is due to its ability to regulate self-reactive T-cells and B-cells. However, according to a new study, an additional vitamin D mechanism may account for this relationship.
Growing evidence suggests toll-like receptors may be partially responsible for the pathogenesis of lupus. Toll-like receptors play a key role in the innate immune system. A type of white blood cell, called leukocytes, expresses toll-like receptors. These receptors activate signaling pathways that stimulates immune responses to attack foreign invaders. However, with lupus, these toll-like receptors may activate autoantigens, resulting in autoimmunity.
New research on vitamin D and immunity
These findings led researchers to analyze the relationship between activated vitamin D and the expression of three variants of toll-like receptors: TLR3, TLR7 and TLR9. The TLR3 and TLR7 are located inside the cell, while the TLR9 is located on the surface of the cell. In particular, TLR7 may contribute to the development of autoimmune disorders.
This study included twenty individuals with SLE and 20 age and sex-matched controls. All patients with SLE included in the analysis visited the Rheumatology Research Center of the Ghaem Hospital, Mashhad, Iran. The researchers obtained cell cultures of the participants white blood cells. Next, they observed gene expressions levels of the toll-like receptors in cultures containing activated vitamin D and those without.
Lupus patients experienced an upregulation of TLR7 and TLR9 levels compared to healthy controls. However, incorporating vitamin D3 (50 nM) in the cell cultures resulted in a significant downregulation of TLR3 (p = 0.03), TLR7 (p = 0.0001) and TLR9 (p = 0.007) expression among SLE patients compared to controls.
The researchers concluded,
“The results of the current study suggest that vitamin D3 could exert some of its immunomodulatory effects in SLE patients via affecting the expression levels of some TLRs.”