Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation.

Abstract

Myeloid-derived suppressor cells (MDSC) are pathologically activated and relatively immature myeloid cells, which are implicated in the immune regulation of many pathologic conditions1,2. Phenotypically and morphologically MDSC are similar to neutrophils (PMN-MDSC) and monocytes (M-MDSC). However, they have potent suppressive activity, a distinct gene expression profile, and biochemical characteristics3. None or very few MDSC are observed in steady state physiological conditions. Therefore, until recently, accumulation of MDSC was considered as a consequence of pathological process or pregnancy. Here, we report that MDSC with a potent ability to suppress T cells are present during the first weeks of life in mice and humans. MDSC suppressive activity was triggered by lactoferrin and mediated by nitric oxide, PGE2, and S100A9/A8 proteins. Newborn MDSC had a transcriptome similar to that of tumor MDSC, but with a strong up-regulation of an antimicrobial gene network and had potent antibacterial activity. MDSC played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSC in infants with very low-weight, which are prone to the development of NEC, had lower MDSC levels and suppressive activity than infants with normal weight. Thus, the transitory presence of MDSC may be critical for regulation of inflammation in newborns.