birth due to the pulmonary congestion and heart failure caused by a patent ductus arteriosus. The ductus operates in the fetus to shunt blood from the pulmonary artery to the proximal descending aorta thereby allowing blood from the heart's right ventricle to bypass the fetus's non-functioning lungs. The ductus must close at birth to allow blood flow into the lungs. In mice, this is accomplished by turning off the mechanism which maintains the ductus's patency. Continuous activation of EP4 by PGE2 keeps the ductus open in the fetus; at birth, however, levels of EP4 and PGE2 in the smooth muscle cells and media in mouse ductus fall. This closes the ductus thereby establishing normal post-fetal circulation of blood through the lungs. Based on studies using EP receptor agonists and receptor antagonists, EP2 in mice and, at least in lambs, EP3 may play minor parts in maintaining patency of the ductus. These studies also appear relevant to humans: nonsteroidal anti-inflammatory drugs, particularly indomethacin, are used to reduce prostaglandin production and thereby close the ductus in neonates, infants, and older patients with Patent ductus arteriosus; furthermore, prostaglandins or their analogs are used to keep the ductus open in neonates with congenital heart defects such as Transposition of the great arteries until corrective surgery can be performed (see Ductus arteriosus#Disorder: Patent ductus arteriosus). To allow further studies of EP4 function, colonies obtained by cross-breeding the 5% of mice surviving EP4 deletion are used. Inflammation Activation of EP4 suppresses the production of IL-12p70 and increases IL-23 thereby promoting development of IL-17-producing Th17 cells, a subset of pro-inflammatory T helper cells that serves to maintain mucosal barriers, clear mucosal surfaces of pathogens, and contribute to autoimmune and inflammatory disorders. Its activation also: a) supports the development of Regulatory T cells (i.e. suppressor T cells that modulate the immune system to maintain tolerance to self-antigens and prevent autoimmune disease); b) stimulate Dendritic cells (i.e. antigen-presenting cells located primarily in the skin and mucus membranes) to mature, migrate, and direct the early stage of immune responses; c) inhibit antibody-producing B cells from proliferating; d) suppresses the development of Atherosclerosis plaques by promoting the death (i.e. apoptosis) of plaque-bound pro-inflammatory macrophages; e) increases the survival of neurons in an inflammation-based model of Alzheimer's disease; f) increases local arteriole and capillary blood flow to cause, for example, site-specific signs of inflammation such as redness, heat, and swelling in rodent