Immune and metabolic shifts during neonatal development reprogram liver identity and function

The liver as a nursery for leukocytes

“…From the third week after birth on, the immune cell profile completely changes, displaying a significant reduction in the number of myeloid cells and an increase in lymphoid cells, including B, T, NK, and NKT cells. These differences were initially found using high‐dimensional immunophenotyping techniques (mass cytometry), and confirmed by microscopy in mice and in human biopsies . Furthermore, a different CX3CR1‐expressing cell compartmentalization is observed from neonates to adults.…”

“…Newborns present high sensitivity to infectious agents with higher rates of mortality, as demonstrated by infections with HIV, Escherichia coli , and Plasmodium falciparum as well as the high mortality rate due to sepsis in preterm . This susceptibility to infections can perhaps be explained by a persistence of regulatory events after birth that support maternal‐fetal tolerance, immaturity of neonatal immune system, and also the absence of intestinal microbiota that are crucial for the establishment of a phenomenon described as colonization resistance . Neonates lack a preexisting immune memory and have a reduced number of immune cells .…”

“…The hematopoietic foci persist up to 2 weeks of life after which liver hematopoiesis is completely replaced by the BM. Hepatic architecture becomes similar to the adult liver and morphologic maturation is completed by the age of 4 weeks in rats and mice and 5 years in humans . However, the regulatory mechanisms underlying this remodeling are not yet well understood.…”

“…It has been recently shown that granulocytes are the main hepatic immune cell population in the neonatal liver. Moreover, there is a large population of monocytes, immature B cells, and immature monocytes/macrophages . From the third week after birth on, the immune cell profile completely changes, displaying a significant reduction in the number of myeloid cells and an increase in lymphoid cells, including B, T, NK, and NKT cells.…”

“…Furthermore, a different CX3CR1‐expressing cell compartmentalization is observed from neonates to adults. It is initially scattered inside the organ and, with the development, becomes restricted to the subcapsular compartment and around large vessels …”