H2R signaling maintains neutrophil homeostasis

H2R deficiency accelerated progression of colitis-associated colon tumors. To identify precise expression pattern of H2R in immune cells, we performed quantitative RT-PCR and revealed that H2R is highly expressed in neutrophils. In mice, H2R deficiency significantly promoted infiltration of neutrophils into both inflammation sites and colon tumors. To precisely elucidate the downstream effects of H2R activation in neutrophils, low-density (LDNs) and high-density (HDNs) neutrophils were enriched from casein-elicited peritoneal cells of wild type and H2R deficient mice, and extracted total RNA were subjected to RNA sequencing. H2R-deficient HDNs not only presented more pro-inflammatory features through NF-kB and MAPK pathways, but also significantly suppressed T cell proliferation, which is essential for cellular immunity. On the other hand, LDNs with no H2R activation displayed a more immature phenotype compared to WT LDNs, with enhanced MYC pathway downstream expressions and a reduced expression of the maturation marker TLR4. RNA-seq of H2R deficient and wildtype low density and high density neutrophils.