New effect on immune system of Vitamin D3

Catherine Hawrylowicz and colleagues, at King's College London, United Kingdom, have now provided new insight into how drugs that stimulate TLR9 might be beneficial, by showing that they inhibit the function of a population of human immune cells known as IL-10–secreting Tregs.

Tregs are immune cells able to dampen ongoing immune responses. They help prevent the immune system from attacking cells and tissues of the body (i.e., they help prevent autoimmue diseases such as rheumatoid arthritis) as well as innocuous inhaled substances (i.e., they help prevent allergy). They therefore have immense clinical potential. In the study, TLR9 was found to be highly expressed by a defined population of human Tregs that produce the soluble antiinflammatory factor IL-10.

Specifically, IL-10–secreting Tregs induced in the presence of a form of Vitamin D known as 1-alpha,25VitD3. In vitro, induction of TLR9 was mainly regulated by 1-alpha,25VitD3, and humans that ingested 1-alpha,25VitD3 were found to have more T cells expressing TLR9 and producing IL-10. Importantly, stimulation of TLR9 on 1-alpha,25VitD3-induced IL-10–secreting Tregs eliminated their ability to suppress immune responses in vitro.

The authors therefore suggest that TLR9 could be used to monitor the generation of 1-alpha,25VitD3-induced IL-10–secreting Tregs in patients with allergy, where they are likely to be beneficial. Further, this effect might help explain the beneficial effects of the TLR9 stimulatory drugs being developed to boost the efficiacy of cancer immunotherapies and vaccines.

By Journal of Clinical Investigation