R-spondin 2 mediates neutrophil egress into the alveolar space through increased lung permeability.

Abstract

Objective R-spondin 2 (RSPO2) is required for lung morphogenesis, activates Wnt signaling, and is upregulated in idiopathic lung fibrosis. Our objective was to investigate whether RSPO2 is similarly important in homeostasis of the adult lung. While investigating the characteristics of bronchoalveolar lavage in RSPO2-deficient (RSPO2-/-) mice, we observed unexpected changes in neutrophil homeostasis and vascular permeability when compared to control (RSPO2+/+) mice at baseline. Here we quantify these observations to explore how tonic RSPO2 expression impacts lung homeostasis. Results Quantitative PCR (qPCR) analysis demonstrated significantly elevated myeloperoxidase (MPO) expression in bronchoalveolar lavage fluid (BALF) cells from RSPO2-/- mice. Likewise, immunocytochemical (ICC) analysis demonstrated significantly more MPO+ cells in BALF from RSPO2-/- mice compared to controls, confirming the increase of infiltrated neutrophils. We then assessed lung permeability/barrier disruption via Fluorescein Isothiocyanate (FITC)-dextran instillation and found a significantly higher dextran concentration in the plasma of RSPO2-/- mice compared to identically treated RSPO2+/+ mice. These data demonstrate that RSPO2 may be crucial for blood-gas barrier integrity and can limit neutrophil migration from circulation into alveolar spaces associated with increased lung permeability and/or barrier disruption. This study indicates that additional research is needed to evaluate RSPO2 in scenarios characterized by pulmonary edema or neutrophilia.

Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection

“…This body of work supports vaginal epithelial cells to be the key source of IL-33-mediated type 2 immunity in the FGT during co-infection. Recent studies have identified myeloid sources of IL-33 to play roles in downregulating mucosal inflammation (Hung et al, 2020a(Hung et al, , 2020bJackson et al, 2020;Sell et al, 2020). The findings we present here do not currently suggest a role for cells other than epithelial cells as a contributing source of IL-33.…”

A novel gene-by-environment quantitative trait locus on mouse chromosome 15 underlies susceptibility to acute ozone-induced lung injury

“…recently examined the consequences of Rspo2 conditional deletion in adult mice. They reported that Rspo2 loss caused lung neutrophilia via a disrupted lung endothelial barrier (68). While there are no variants within this gene, we noted multiple noncoding variants within the in/near the gene, and its function is in alignment with features of the pathology caused by O3 exposure.…”