Immune-modulatory Effects of Vitamin DSubmit Manuscript on this topic
Vitamin D plays an essential role in bone development. However, recent studies are beginning to uncover its role as a modulator of the immune system. Several reports have shown associations between vitamin D deficiency and the incidence as well as the severity of chronic inflammatory diseases such as cardiovascular disease, inflammatory bowel disease, asthma and chronic obstructive pulmonary disease (COPD). Consistent with this, Vitamin D supplementations have been shown to reduce the severity of and inflammation markers in chronic inflammatory diseases. Low vitamin D levels have also been associated with the incidence of autoimmune diseases such as Rheumatoid Arthritis (RA), Multiple Sclerosis (MS) and Systemic Lupus Erythematosus (SLE). Low vitamin D status is also common in genetic diseases such as cystic fibrosis, while increased vitamin D levels are associated with improved lung function. Finally, low vitamin D status has been shown to be a risk factor for infectious diseases such as Tuberculosis (TB).
At the cellular level, vitamin D exerts anti-inflammatory effects on immune cells that express the vitamin D receptor (VDR) such as monocytes, macrophages, and T lymphocytes, which in turn shapes the immune response during the onset of inflammation and infection and following vaccination. Vitamin D exerts these anti-inflammatory effects by reducing pro-inflammatory cytokine production from macrophages and T cells. Sufficient levels of vitamin D have also been shown to regulate T cell proliferation by controlling T cell antigen receptor and T cell activation as well as enhancing the phagocytic activity of macrophages. In cases of autoimmune diseases, low vitamin D levels are associated with increased B cell proliferation and autoantibody production. At the molecular level, the hormonally-active form of vitamin D (α1,25 dihydroxyvitamin D3) regulates the expression of vitamin D responsive genes that can lead to differential regulation of signaling pathways in immune cells. For example, vitamin D positively regulates iron homeostasis and erythropoiesis via the iron-hepcidin-ferroportin axis. During infections such as TB, Vitamin D induces the expression of cathelicidin (LL-37), a host defense peptide that enhances the bactericidal activity of immune cells like macrophages, thereby limiting the growth of mycobacteria that causes TB. Furthermore, LL-37 exerts anti-inflammatory effects via its ability to neutralize bacterial molecules like endotoxins and capsular polysaccharides that activate TLR signaling pathways, consequently inhibiting the release of pro-inflammatory mediators from macrophages. Finally, Vitamin D has also been shown to induce the expression of autophagy-related genes in immune cells, thereby regulating immune cell survival during host defense, inflammation and cancer.
In this Research Topic, we welcome the submission of Original Research Articles, Reviews, Clinical Trial Articles and Perspectives. This collection will cover the multiple facets of the immuno-modulatory effects of Vitamin D, including, but not limited to:
(i) Mechanisms by which vitamin D modulates cellular responses in:
• Innate immune cells such as macrophages and dendritic cells
• Adaptive immune cells such as T lymphocytes
(ii) Regulation of Autophagy by Vitamin D in innate and adaptive immune cells
(iii) Immune-modulatory effects of vitamin D in bacterial, viral and fungal infections
(iv) Immune-modulatory effects of vitamin D in cancer
(v) Immune-modulatory effects of vitamin D in inflammatory and autoimmune diseases