Integrin CD11c regulates B cell homeostasis.

CD11c is widely known as a cell surface marker for dendritic cells, but we recently showed that it regulates neutrophil and T cell functions. Because we found that CD11c knockout (KO) mice had lower blood B cell counts, we characterized B cell profile in developmental stages. We found that CD11c KO recirculating and mature B cells was significantly fewer compared with wild type, associated with exaggerated proliferation and apoptosis. Because they did not express CD11c, we sought for the possibility of CD11c-mediated non-intrinsic regulation of B cell proliferation and apoptosis. Here we hypothesized that dendritic cells, major cells expressing CD11c would regulate B cells indirectly. The proteomics of dendritic cells cultured in vitro indicated the downregulation of macrophage migration inhibitory factor (MIF). Less MIF was also confirmed by ELISA. Furthermore, plasma MIF level was significantly lower in naïve CD11c KO mice. Because MIF regulates B cell survival, we demonstrated a novel regulatory mechanism of naïve B cells via CD11c.

Neutrophil extracellular traps formation is associated with postoperative complications in neonates and infants undergoing congenital cardiac surgery.

Pediatric patients with congenital heart diseases (CHD) often undergo surgical repair on cardiopulmonary bypass (CPB). Despite a significant medical and surgical improvement, the mortality of neonates and infants remains high. Damage-associated molecular patterns (DAMPs) are endogenous molecules released from injured/damaged tissues as danger signals. We examined 101 pediatric patients who underwent congenital cardiac surgery on CPB. The mortality rate was 4.0%, and the complication rate was 31.6%. We found that neonates/infants experienced multiple complications most, consistent with the previous knowledge. Neonates and infants in the complication group had received more transfusion intraoperatively than the non-complication arm with lower maximum amplitude (MA) on rewarming CPB thromboelastography (TEG). Despite TEG profiles were comparable at ICU admission between the two groups, the complication arm had higher postoperative chest tube output, requiring more blood transfusion. The complication group showed greater neutrophil extracellular traps (NETs) formation at the end of CPB and postoperatively. Plasma histones and high mobility group box 1 (HMGB1) levels were significantly higher in the complication arm. Both induced NETs in vitro and in vivo . As histones and HMGB1 target Toll-like receptor (TLR)2 and TLR4, their mRNA expression in neutrophils was upregulated in the complication arm. Taken together, NETs play a major role in postoperative complication in pediatric cardiac surgery and would be considered a target for intervention. Key points: Neonates and infants showed highest postoperative complications with more upregulation of inflammatory transcriptomes of neutrophils.Neonates and infants with organ dysfunction had more NETs formation with higher plasma histones and HMGB1 levels.