The role of vitamin D in the fate and function of tissue antigens
Staff: Robert Busch
Vitamin D, long known for its roles in the growth and maintenance of bone health, is increasingly recognised as a regulator of immune function. Made in sun-exposed skin or taken in with food, such as fatty fish, vitamin D regulates hundreds of genes with immune functions. Vitamin D deficiency is common in people with severe COVID-19 complications and patients with many autoimmune diseases; low vitamin D has been strongly implicated as a risk factor for the development of multiple sclerosis (MS), an autoimmune disease affecting long nerve fibres. Because of its manifold actions, the consequences of vitamin D status for immune physiology remain murky. This ongoing project, with past funding by the MS Society and the MS International Federation, focusses on the effects of vitamin D on the way in which tissue antigens function in the immune system. They normally allow T cells (white blood cells involved in surveillance against infectious agents, which cause damage in autoimmune diseases) to detect evidence of infection on the surfaces of other cells in the human body, while also serving to maintain the T cells in a state of immune tolerance. They do this by capturing fragments of other proteins (normally representing self, but including fragments from disease-causing organisms during infections) inside cells and displaying them on their surface, where T cells may inspect them. This involves a complex journey of the tissue antigens through the cell, and the capture of protein fragments at defined steps on this journey. We have traced the effects of vitamin D on different stages of this process in cell lines and are further exploring the possibility that this may be one of the reasons for its protective role in autoimmunity. In this research, we also develop and apply new methods for studying how genetic variation of tissue antigens influences their responsiveness to vitamin D.
Nakul Shah (PhD, 2019) and Robert Busch study vitamin D effects on tissue antigens using flow cytometry