Developmental vitamin D3 deficiency induces alterations in immune organ morphology and function in adult offspring.

Vitamin D3 deficiency and insufficiency are common in women of child-bearing age. This may be cause for concern because vitamin D3 is a well known regulator of immune function and epidemiological evidence has suggested that immune disorders, including autoimmune diseases, could have developmental origins. However, it is not known whether a developmental deficiency in vitamin D3 could lead to persistent changes in the immune system in adult offspring. Given the prominence of receptors for vitamin D3 within immune cells we hypothesised that the developmental absence of vitamin D3 may alter thymic development and thus produce associated functional changes in T cells. We have developed a model of developmental vitamin D3 (DVD) deficiency in Sprague-Dawley rats, in which the vitamin D3 deficiency is transient and restricted to gestation. First we demonstrate that DVD deficiency induced an increase in central but not peripheral immune organ size. Second when stimulated, lymphocytes from DVD-deficient rats exhibit a pro-inflammatory phenotype. This is the first study to show that a transient vitamin D3 deficiency restricted to gestation can persistently alter aspects of immune phenotype and function in the adult offspring. Given an increased incidence of vitamin D3 deficiency in women of child-bearing age these findings may be highly relevant for autoimmune disorders with a developmental basis.