Secreted PLA(2) group X orchestrates innate and adaptive immune responses to inhaled allergen
JCI INSIGHT
Authors: Nolin, James D.; Lai, Ying; Ogden, Herbert Luke; Manicone, Anne M.; Murphy, Ryan C.; An, Dowon; Frevert, Charles W.; Ghomashchi, Farideh; Naika, Gajendra S.; Gelb, Michael H.; Gauvreau, Gail M.; Piliponsky, Adrian M.; Altemeier, William A.; Hallstrand, Teal S.
Abstract
Phospholipase A(2) (PLA(2)) enzymes regulate the formation of eicosanoids and lysophospholipids that contribute to allergic airway inflammation. Secreted PLA(2) group X (sPLA(2)-X) was recently found to be increased in the airways of asthmatics and is highly expressed in airway epithelial cells and macrophages. In the current study, we show that allergen exposure increases sPLA(2)-X in humans and in mice, and that global deletion of Pla2g10 results in a marked reduction in airway hyperresponsiveness (AHR), eosinophil and T cell trafficking to the airways, airway occlusion, generation of type-2 cytokines by antigen-stimulated leukocytes, and antigen-specific immunoglobulins. Further, we found that Pla2g10(-/-) mice had reduced IL-33 levels in BALF, fewer type-2 innate lymphoid cells (ILC2s) in the lung, less IL-33-induced IL-13 expression in mast cells, and a marked reduction in both the number of newly recruited macrophages and the M2 polarization of these macrophages in the lung. These results indicate that sPLA(2)-X serves as a central regulator of both innate and adaptive immune response to proteolytic allergen.
Mating to Intact, but Not Vasectomized, Males Elicits Changes in the Endometrial Transcriptome: Insights From the Bovine Model
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Authors: Recuero, Sandra; Sanchez, Jose Maria; Mateo-Otero, Yentel; Bages-Arnal, Sandra; McDonald, Michael; Behura, Susanta K.; Spencer, Thomas E.; Kenny, David A.; Yeste, Marc; Lonergan, Pat; Fernandez-Fuertes, Beatriz
Abstract
An appropriate female reproductive environment is essential for pregnancy success. In several species, including mice, pigs and horses, seminal plasma (SP) components have been shown to modulate this environment, leading to increased embryo viability and implantation. Due to the characteristics of mating in the aforementioned species, SP comes into direct contact with the uterus. However, it is questionable whether any SP reaches the uterus in species that ejaculate inside the vagina, such as humans and cattle. Hence, we hypothesized that sperm, perhaps acting as a vehicle for SP factors, play a more important role in the modulation of the maternal uterine environment in these species. In addition, changes elicited by SP and/or sperm may originate in the vagina and propagate to more distal regions of the female reproductive tract. To test these hypotheses, a bovine model in which heifers were mated to intact or vasectomized bulls or were left unmated was used. RNA-sequencing of endometrial samples collected 24 h after mating with a vasectomized bull did not reveal any differentially expressed genes (DEGs) in comparison with control samples. However, the endometrium of heifers mated with intact bulls exhibited 24 DEGs when compared to heifers mated with vasectomized bulls, and 22 DEGs when compared to unmated control heifers. The expression of a set of cytokines (IL6,IL1A,IL8, andTNFA) and candidate genes identified in the endometrial RNA-sequencing (PLA2G10,CX3CL1,C4BPA,PRSS2,BLA-DQB, andCEBPD) were assessed by RT-qPCR in the vagina and oviductal ampulla. No differences in expression of these genes were observed between treatments in any region. However, mating to both intact and vasectomized bulls induced an increase inIL1AandTNFAexpression in the vagina compared to the oviduct. These data indicate that sperm, but not secretions from the accessory glands alone, induce modest changes in endometrial gene expression after natural mating in cattle. However, it is not clear whether this effect is triggered by inherent sperm proteins or SP proteins bound to sperm surface at the time of ejaculation.