Distinct functional programming of human fetal and adult monocytes.

Authors:
Krow-Lucal ER, Kim CC, Burt TD, McCune JM
In:
Source: Blood
Publication Date: (2014)
Issue: 123(12): 1897-904
Research Area:
Basic Research
Cells used in publication:
Monocyte, human
Species: human
Tissue Origin: blood
Bone Marrow, Human, Unprocessed
Species: human
Tissue Origin: bone marrow
Mononuclear, bone marrow, human
Species: human
Tissue Origin: bone marrow
Culture Media:
Abstract
Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-? (IFN-?), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-?, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-? signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.