NIH – Understanding the Early Development of the Immune System (R01 – Clinical Trial Not Allowed)

October 31, 2017 by School of Medicine Webmaster

There is direct contact between fetal and maternal tissues during pregnancy. The uterine maternal tissue is remodeled into a form that is compatible with both organisms. This interplay between the two is orchestrated in such a way that the developing fetus although semi-allogeneic is not rejected by the mother. There is ample evidence to show that the mother is exquisitely aware of the foreignness of the fetus but in a myriad of ways does not reject the fetus. It has also been established that the maternal cellular and non-cellular components are in intimate contact with the prenatal milieu before and after blood flow is established via the umbilical arteries after the first trimester of pregnancy. It is also well established that fetal cellular and non-cellular elements are found in the maternal tissues and circulation.

Since components including cells of the immune system develop early in gestation and are essential for the normal development of the fetus through pregnancy, and evolve with in utero environmental exposures it would be of interest to evaluate the inter-communication that occurs between the mother and fetus throughout pregnancy and after birth, especially in the context of infectious disease.

It has been shown that cells of the immune system develop early in gestation. B lymphocytes develop in the fetal liver by week 9 and are in the spleen and circulate by week 12 and T lymphocytes leave the thymus at about week 14 and travel to the spleen. It has also been suggested that all the elements of the mature immune system are functional in fetal life but that the robustness of the system is tempered by maternal and perhaps placental toning. There is mature antigen handling by monocytes by birth.

This FOA encourages research on the immune system of the mother/placenta in infection/health and its impact on the development of the fetal immune system, including its function during gestation and beyond. To interrogate this in utero communication system, it will be necessary to utilize new techniques that can measure low cell numbers with accuracy and use systems that can easily model the human system. Systems that look at the fetal-maternal interactions as well as maternal fetal interactions are encouraged.

Areas of interest include, but are not limited to:

  • Studies that explore the first maternal/fetal communications during gestation and the impact on the developing fetal immune system;
  • Studies that explore whether maternal factors can alter or modulate signaling in the very early immune system, including inflammatory signals;
  • Research to explore the elements, including cytokines, cells, virus, prion, and exosomes, that may deliver immune modulating signals involved in prenatal/ maternal communications;
  • Studies focused on cellular, and molecular maternal/fetal trafficking during very early immune system development in infection and health;
  • Research on the timing, development and maturation of immune system cells and cytokines, in infectious disease;
  • Studies of fetal innate and cellular component development and susceptibility to maternal/placental infection;
  • Studies to examine the maternal seeding and evolution of the fetal microbiome in infection/health and the impact on the developing brain;
  • Studies to explore maternal influences including medication use on in-utero microbiome colonization of the fetus on the downstream development of immune tolerance or hypersensitivity;
  • Studies of the maternal and infant in utero immune response to select immunogens and infectious agents;
  • Studies to test whether a subset of fetal immune cells or components can be activated to respond to select immunogens for vaccine development.

Deadlines:  April 4, 2018, December 5, 2018, April 5, 2019, December 5, 2019

URL:  https://grants.nih.gov/grants/guide/pa-files/PAR-18-333.html

Filed Under: Funding Opportunities