Research sheds light on the function of MDSCs in newborns. [MedlinePlus]
Research sheds light on the function of MDSCs in newborns. [MedlinePlus]

Scientists from the Wistar Institute and Sun Yat-sen University in China report that they characterized the transitory presence of myeloid-derived suppressor cells (MDSCs) in mouse and human newborns. They say their study (“Transitory Presence of Myeloid-Derived Suppressor Cells in Neonates Is Critical for Control of Inflammation”), published in Nature Medicine, sheds light on the critical role these cells play in the regulation of inflammation in the early stages of life.

“Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy,” write the investigators.

“Here, we report that MDSCs 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 and S100A8 proteins. MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with strong upregulation of an antimicrobial gene network, and had potent antibacterial activity. MDSCs played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low weight, who are prone to NEC, had lower MDSC levels and suppressive activity than did infants with normal weight. Thus, the transitory presence of MDSCs may be critical for regulation of inflammation in newborns.”

“Our research sheds light on the function of MDSCs in newborns, suggesting that they are critical for the regulation of inflammation during the first weeks of life,” said Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor and program leader of the Immunology, Microenvironment and Metastasis Program at Wistar. “We also revealed a physiological role of MDSCs expansion, which was widely considered to be driven by pathological conditions or pregnancy, broadening the importance of MDSCs in the immune system.”

Dr. Gabrilovich and colleagues compared the proportion of MDSCs in newborn, adult, and postpartum mice. Those that were three to 10 days old had substantially higher numbers of these cells with a potent immunosuppressive ability and the proportion gradually decreased to levels comparable to those in adult mice by the end of the second week of life.

Analyzing the transcription profile of MDSCs from newborn mice, the team observed increased expression of genes that are critical for the immunosuppressive functions of these cells. Mechanistically, they demonstrated that the accumulation of MDSCs is linked with milk feeding, as it depends on lactoferrin, a milk component with potent immunoregulatory activity, which can induce upregulation of these genes.

The researchers also found that MDSCs are important for the control of inflammation in newborns. In fact, human newborns with normal birth weight had a significantly higher proportion of MDSCs and higher immunosuppressive activity compared with adults as well as infants with low birth weight. These infants are at a higher risk for development of pathological inflammatory conditions, such as NEC, a condition that causes inflammation of the intestine and may put the infant at risk for developing potentially life-threatening infections. 

“Our findings demonstrate that MDSCs reduce inflammation and increase survival in a model of NEC, thus suggesting that MDSCs not only can be present in healthy individuals but also could be an important protection mechanism evolved in response to the microbial colonization of the gut that takes place during the first days of life,” said Dr. Gabrilovich.

“Based on our data, MDSCs may be used as a potential therapeutic target for treating NEC and other inflammatory conditions in infants,” added Michela Perego, Ph.D., an associate staff scientist in the Gabrilovich Lab and co-first author of the study. “Our finding that accumulation of MDSCs depends on lactoferrin may also provide a rationale as to why feeding infants human milk versus formula has been shown to reduce the risk of NEC.”








This site uses Akismet to reduce spam. Learn how your comment data is processed.