Increased monocytic CD14+HLADRlow/− myeloid-derived suppressor cells in obesity

Abstract

Obesity is associated with numerous immunological disorders. The present study investigated the proportion and phenotype of myeloid‑derived suppressor cells (MDSCs) in the plasma of obese subjects and the association of these cells with the level of liver enzymes. Certain features of the immune response in obese subjects were examined by analyzing the expression of T cell receptor‑ζ (TCRζ) molecules on the surface of T cells. The expression and secretion of S100A9, a possible marker for MDSCs, were detected in the peripheral blood of obese subjects and compared with levels in lean controls. Results showed that the percentage of monocytic MDSCs, with the phenotype CD33+CD11b+CD14+HLADRlow/‑, was significantly increased in obese subjects compared with lean controls. The circulating level of monocytic MDSCs was positively correlated with the levels of liver enzymes in serum. The expression of the TCRζ molecule in the resting T cells was significantly lower in obese individuals than that of lean controls. The expression of S100A9 was detected in the majority of monocytes in peripheral blood mononulear cells, but no difference was identified in the frequency of CD14+S100A9+ cells between the obese and lean groups. However, the plasma level of S100A8/9 was significantly increased in obese compared with lean subjects. These observations suggested that the increased frequency of CD33+CD11b+CD14+HLADRlow/‑ cells may be responsible for the impaired T‑cell function and liver injury observed in obesity.

Immunosuppressive myeloid-derived suppressor cells are increased in splenocytes from cancer patients

“…Other studies have shown an association of peripheral MDSCs with age [29] and obesity [30, 31], risk factors associated with poorer outcomes in pancreatic cancer patients [32]. We were unable to correlate the frequency of MDSC in the spleen with these clinical characteristics.…”

In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock

“…In adults, S100A8/S100A9 are strong positive regulators of MDSCs (11)(12)(13)(14)(15)(16)(17)(18)(19). Assuming that neonatal DR 2 Mos, like adult DR 2 Mos, represent Mo-MDSCs, we speculated that their expansion in newborns is due to the previously demonstrated high perinatal release of S100A8/S100A9 (6).…”

“…We previously showed that newborn Mos massively release the alarmins S100A8 and S100A9 upon birth (6). Because S100A8/ S100A9 are major regulators of MDSCs in adults (11)(12)(13)19), we initially hypothesized that S100A8/ S100A9 cause an expansion of Mo-MDSCs that might contribute to an immunocompromised state in neonates.…”

“…They are specifically expressed by myeloid cells and have proinflammatory as well as tolerizing effects on different innate immune cells, especially monocytes (Mos) (6-10). In adults, S100A8/ S100A9 are well-known positive regulators of the number and function of myeloid-derived suppressor cells (MDSCs) by acting on hematopoietic progenitor cells (11)(12)(13)(14)(15)(16)(17)(18)(19). Whether theses alarmins also have MDSCpromoting effects in neonates has not previously been examined.…”

Obesity as an immune-modifying factor in cancer immunotherapy

“…In humans, there are few studies examining the impact of obesity on MDSC accumulation. However, a small cohort study from Bao and colleagues observed an increase in MDSCs in the peripheral blood of overweight/obese male Chinese subjects (BMI > 25 kg/m 2 ) compared to lean male healthy controls (BMI < 25 kg/m 2 ) …”