Placental extract suppresses mouse models of autoimmunity (83.4)

Abstract

Abstract Pregnancy is known to modulate many autoimmune diseases. For example, autoimmune thyroiditis improves during pregnancy, and autoimmune hypophysitis presents during this period. The mechanisms underlying the effect of pregnancy on autoimmunity remain unknown. To determine whether placental proteins influence autoimmunity, we used a mouse model of experimental autoimmune hypophysitis (EAH). Here we report that co-immunization of mice with placental extract and pituitary extract, significantly decreased EAH incidence, severity, and antibody titers. Disease suppression was specific to the placenta; liver or muscle extracts were incapable of suppressing disease. Disease suppression, however, was not specific to EAH: co-immunization of placental extract with thyroglobulin, similarly decreased antibody titers. Immunization with pituitary extract during early or late pregnancy and administration of non-emulsified placental extracts were ineffective in suppressing EAH. Suppression of EAH was only observed when the placental extract was at the same location as the immunogen. Placental extracts were found to contain high levels of soluble TNF receptor one (sTNFR1). Furthermore, a placental extract deficient in TNFR1 was incapable of suppressing EAH, suggesting that sTNFR1 may be responsible for the placental-mediated suppression of EAH. These results suggest that a placental component, possibly sTNFR1, is capable of dampening the immune response to a co-injected immunogen.