Dynamic Changes of NCR− Type 3 Innate Lymphoid Cells and Their Role in Mice with Bronchopulmonary Dysplasia

Cai, Jiayu; Lü, Hongyan; Su, Zhaoliang; Mi, Lanlan; Xu, Suqing; Xue, Zhengyang

doi:10.1007/s10753-021-01543-7

Cited by 5 publications

(3 citation statements)

References 40 publications

(54 reference statements)

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“…IL-17 plays an important role in instigating and/or exacerbating fetal inflammatory responses that increase neonatal morbidities and mortalities associated with sepsis and BPD 26 . In experimental BPD, IL-17 was shown to be secreted by type 3 innate lymphoid cells, and it can aggravate lung inflammation 27 . High TNF-α levels were detected in preterm infants with BPD 28 and neonatal mice with experimental BPD 29 .…”

Section: Discussionmentioning

confidence: 99%

GSDMD deficiency ameliorates hyperoxia-induced BPD and ROP in neonatal mice

Sonny

Yuan

Chen

et al. 2023

Sci Rep

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Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are among the most common morbidities affecting extremely premature infants who receive oxygen therapy. Many clinical studies indicate that BPD is associated with advanced ROP. However, the mechanistic link between hyperoxia, BPD, and ROP remains to be explored. Gasdermin D (GSDMD) is a key executor of inflammasome-induced pyroptosis and inflammation. Inhibition of GSDMD has been shown to attenuate hyperoxia-induced BPD and brain injury in neonatal mice. The objective of this study was to further define the mechanistic roles of GSDMD in the pathogenesis of hyperoxia-induced BPD and ROP in mouse models. Here we show that global GSDMD knockout (GSDMD-KO) protects against hyperoxia-induced BPD by reducing macrophage infiltration, improving alveolarization and vascular development, and decreasing cell death. In addition, GSDMD deficiency prevented hyperoxia-induced ROP by reducing vasoobliteration and neovascularization, improving thinning of multiple retinal tissue layers, and decreasing microglial activation. RNA sequencing analyses of lungs and retinas showed that similar genes, including those from inflammatory, cell death, tissue remodeling, and tissue and vascular developmental signaling pathways, were induced by hyperoxia and impacted by GSDMD-KO in both models. These data highlight the importance of GSDMD in the pathogenesis of BPD and ROP and suggest that targeting GSDMD may be beneficial in preventing and treating BPD and ROP in premature infants.

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Section: Discussionmentioning

confidence: 99%

GSDMD deficiency ameliorates hyperoxia-induced BPD and ROP in neonatal mice

Sonny

Yuan

Chen

et al. 2023

Sci Rep

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“…Recent studies have found that IL-17 A level is significantly upregulated and the IL-17 signaling pathway is significantly activated in the external circulation of children with BPD [ 10 , 34 , 35 ]. In the BPD mouse model, the expression of Th17 cells was enhanced in lung, demonstrating strong pro-inflammatory properties and resistance to Treg mediated inhibition [ 13 , 37 , 38 ]. During the critical developmental window of premature infants, the Th17 biased pro-inflammatory response caused by intrauterine inflammation weakens the immune program, leading to “dysfunctional immune activation“[ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…This was accompanied by an increase in the IL-6 concentration in neonatal tracheal aspirates, which was linked to the progression of BPD [ 11 , 12 ]. Our previous studies found that that lung inflammation was significantly reduced in BPD mice after the administration of anti-IL-17 neutralizing antibody [ 13 ]. Therefore, we concluded that IL-17 and the Th17 cell response play an important role in BPD development.…”

Section: Introductionmentioning

confidence: 99%

ILC2 regulates hyperoxia-induced lung injury via an enhanced Th17 cell response in the BPD mouse model

Zhu

Lü

et al. 2023

BMC Pulm Med

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Backgroud Recent research has focused on the role of immune cells and immune responses in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact mechanisms have not yet been elucidated. Previously, the key roles of type 2 innate lymphoid cells (ILC2) in the lung immune network of BPD were explored. Here, we investigated the role Th17 cell response in hyperoxia-induced lung injury of BPD, as well as the relationship between ILC2 and Th17 cell response. Methods A hyperoxia-induced BPD mouse model was constructed and the pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining. Flow cytometry analysis was conducted to determine the levels of Th17 cell, ILC2 and IL-6+ILC2. The expression levels of IL-6, IL-17 A, IL-17 F, and IL-22 in the blood serum and lung tissues of BPD mice were measured by ELISA. To further confirm the relationship between ILC2 and Th17 cell differentiation, ILC2 depletion was performed in BPD mice. Furthermore, we used immunomagnetic beads to enrich ILC2 and then flow-sorted mouse lung CD45+Lin-CD90.2+Sca-1+ILC2. The sorted ILC2s were injected into BPD mice via tail vein. Following ILC2 adoptive transfusion, the changes of Th17 cell response and lung injury were detected in BPD mice. Results The expression levels of Th17 cells and Th17 cell-related cytokines, including IL-17 A, IL-17 F, and IL-22, were significantly increased in BPD mice. Concurrently, there was a significant increase in the amount of ILC2 and IL-6+ILC2 during hyperoxia-induced lung injury, which was consistent with the trend for Th17 cell response. Compared to the control BPD group, ILC2 depletion was found to partially abolish the Th17 cell response and had protective effects against lung injury after hyperoxia. Furthermore, the adoptive transfer of ILC2 enhanced the Th17 cell response and aggravated lung injury in BPD mice. Conclusions This study found that ILC2 regulates hyperoxia-induced lung injury by targeting the Th17 cell response in BPD, which shows a novel strategy for BPD immunotherapy.

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