TY - JOUR
T1 - IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation
AU - Presicce, Pietro
AU - Park, Chan Wook
AU - Senthamaraikannan, Paranthaman
AU - Bhattacharyya, Sandip
AU - Jackson, Courtney
AU - Kong, Fansheng
AU - Rueda, Cesar M.
AU - DeFranco, Emily
AU - Miller, Lisa A.
AU - Hildeman, David A.
AU - Salomonis, Nathan
AU - Chougnet, Claire A.
AU - Jobe, Alan H.
AU - Kallapur, Suhas G.
PY - 2018/3/22
Y1 - 2018/3/22
N2 - Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1-expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1-dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.
AB - Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1-expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1-dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.
KW - Immunology
KW - Neutrophils
KW - Reproductive Biology
UR - https://www.scopus.com/pages/publications/85063245199
UR - https://www.scopus.com/pages/publications/85063245199#tab=citedBy
U2 - 10.1172/jci.insight.98306
DO - 10.1172/jci.insight.98306
M3 - Article
C2 - 29563340
AN - SCOPUS:85063245199
VL - 3
JO - JCI insight
JF - JCI insight
IS - 6
ER -