Gestational hypothyroxinemia increases the immune response of the progeny that suffers experimental autoimmune encephalomyelitis.

Abstract

Abstract There are more evidences supporting the relevance of a healthy pregnancy over offspring imprinting. This is the case for the maternal endocrine status and the immune system. Hypothyroxinemia (Hpx) is a highly frequent thyroid hormone deficiency condition in pregnant women characterized by low levels of thyroxin (T4) with normal levels of triiodothyronine (T3) and thyroid stimulating hormone (TSH) in the blood. It is known that this condition is asymptomatic for the mother, however it impairs cognition in the offspring. In this work we have shown that the effects of gestational Hpx go beyond the central nervous system by also affecting the immune response. We observed that gestational Hpx increases the immune response in the offspring that suffers experimental autoimmune encephalomyelitis (EAE). EAE is an experimental model used to study multiple sclerosis (MS). We show here that mice C57BL/6 gestated in Hpx induced with EAE suffer earlier and more intense EAE symptoms compared to C57BL/6 mice gestated in euthyroidism. Even though, the population of T regulatory (Treg) cells in the spleen was similar in mice gestated in Hpx and mice gestated in euthyroidism, the Treg cells from mice gestated in Hpx have less capacity to suppress T effector cells and to secret IL-10. Mice gestated in Hpx have high basal levels of TNF-α and IL-17 and present increased brain blood barrier permeability. In this work we analyzed the population of Th-17 and capacity to secret IL-17 from intestine, meninges and spleen in mice gestated in Hpx that suffer EAE. These results are very novel and impact our knowledge of how the immune system of the offspring could be affected by the deficiency of maternal thyroid hormones during gestation.