The Bcl2a1 gene cluster finally knocked out: first clues to understanding the enigmatic role of the Bcl-2 protein A1

Berberich, Ingolf; Hildeman, David

doi:10.1038/cdd.2017.25

Cited by 4 publications

(3 citation statements)

References 11 publications

(11 reference statements)

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“…A recent study reported the presence of natural cytotoxicity receptor expressing innate lymphoid cell-3 (NCR + ILC3) in the decidua and suggest that these NCR + ILC3 may play a role in enhancing neutrophil survival via secretion of CXCL8 and GM-CSF (75). Here, we show that IL-1 signaling is upstream of BCL2A1 induction, which may signal through the PI3K and JAK/STAT pathways (37,73) during intrauterine inflammation. Dysregulated prosurvival of neutrophils is known to exacerbate chronic inflammation (76,77), and therapeutic induction of apoptosis may be a novel antiinflammatory strategy (78).…”

Section: Discussionmentioning

confidence: 54%

See 1 more Smart Citation

IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation

Presicce¹,

Park²,

Senthamaraikannan³

et al. 2018

JCI Insight

127

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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.

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Section: Discussionmentioning

confidence: 54%

“…The most upregulated genes in both rhesus and human chorio-decidua identified a profile of genes known to be expressed by activated neutrophils (Table 1). BCL2A1 (called BFL1 in humans), an inhibitor of apoptosis (37), is one of the highly upregulated genes common to both rhesus and humans.…”

Section: Introductionmentioning

confidence: 99%

IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation

Presicce¹,

Park²,

Senthamaraikannan³

et al. 2018

JCI Insight

127

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“…During IUI, the choriodecidual neutrophils predominantly produce TNFα, IL-8, and MIP-1β/CCL4 (114,116). Although blood neutrophils have a short life-span, neutrophils in the decidua have greatly increased survival, mediated in part by up-regulating anti-apoptotic mediators including Bcl-2 family members (e.g., Bcl2A1, called Bfl-1 in humans) (84,152). Neutrophils can amplify the inflammatory response and neutralize microorganisms by releasing neutrophil extracellular traps (NETs), producing antimicrobial enzymes such as defensins, neutrophil elastase, and myeloperoxidase (MPO), and releasing reactive oxygen species (ROS) (153)(154)(155).…”

Section: Neutrophilsmentioning

confidence: 99%

Immunobiology of Acute Chorioamnionitis

2020

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Acute chorioamnionitis is characterized by neutrophilic infiltration and inflammation at the maternal fetal interface. It is a relatively common complication of pregnancy and can have devastating consequences including preterm labor, maternal infections, fetal infection/inflammation, fetal lung, brain, and gastrointestinal tract injury. In this review, we will discuss current understanding of the pathogenesis, immunobiology, and mechanisms of this condition. Most commonly, acute chorioamnionitis is a result of ascending infection with relatively low-virulence organisms such as the Ureaplasma species. Furthermore, recent vaginal microbiome studies suggest that there is a link between vaginal dysbiosis, vaginal inflammation, and ascending infection. Although less common, microorganisms invading the maternal-fetal interface via hematogenous route (e.g., Zika virus, Cytomegalovirus, and Listeria) can cause placental villitis and severe fetal inflammation and injury. We will provide an overview of the knowledge gleaned from different animal models of acute chorioamnionitis and the role of different immune cells in different maternal-fetal compartments. Lastly, we will discuss how infectious agents can break the maternal tolerance of fetal allograft during pregnancy and highlight the novel future therapeutic approaches.

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