Biology subjects

Fukuoka, A.

Publications and source records attributed to Fukuoka, A..

5 recordsLinked to original sources

bioRxiv2024

Eosinophils promote monocyte to macrophage differentiation and anti-bacterial immunity

Chemokine receptors control cell migration within the body. Here we reveal a novel interaction between eosinophils and monocytes in the bone marrow, indirectly controlled by the atypical chemokine receptor ACKR2. We demonstrate that ACKR2 maintains eosinophil levels within the bone marrow by scavenging CCL11. In the absence of ACKR2, elevated CCL11 leads to increased egress of eosinophils from the bone marrow into the bloodstream. As a result, eosinophil and monocyte interactions are reduced within the bone marrow niche, leading to changes in monocyte gene expression. Monocytes from ACKR2-/- mice are recruited to the tissues but are fundamentally altered in their ability to differentiate into macrophages, in the lung, peritoneal cavity and cavity wall. Bacterial elimination is impaired in ACKR2-/- mice during peritoneal infection. ACKR2 is therefore a key regulator of eosinophil-driven monocyte education in the bone marrow, required for full monocyte differentiation and macrophage function within the tissues.

immunology↗

bioRxiv2023

Induction of plant disease resistance by mixed oligosaccharide elicitors prepared from plant cell wall and crustacean shells

Basal plant immune responses are activated by the recognition of the conserved pathogen-associated molecular patterns (PAMPs), or breakdown molecules released from plants after damage by pathogen infection, so-called danger-associated molecular patterns (DAMPs). While chitin-oligosaccharide (CHOS), a primary component of the fungal cell wall, is most known as PAMP, plant cell wall-derived oligosaccharides, cello-oligosaccharides (COS) from cellulose and xylo-oligosaccharide (XOS) from hemicellulose, are representative DAMPs, which activate signaling steps similar to PAMP-induced immunity to elicit defenses and provide protection against pathogens. In this study, elicitor activities of COS prepared from cotton linters, XOS prepared from corn cobs as well as chitin-oligosaccharide (CHOS) from crustacean shells were comparatively investigated. In Arabidopsis, treatment of COS, XOS or CHOS triggered typical defense responses such as reactive oxygen species (ROS) production, activation of MAP kinases phosphorylation, callose depositions, and activation of the promoter for defense-related transcription factor WRKY33. When COS, XOS and CHOS were used at concentrations with similar activity in inducing ROS production and callose depositions, CHOS was particularly highly potent in activating the MAPK kinases and WRKY33 promoters. Among the COS and XOS with different degrees of polymerization (DP), cellotriose (DP3) and xylotetraose (DP4) showed the highest activity for the activation of WRKY33 promoter. Simultaneous treatment of COS, XOS and CHOS leads to a strong transcriptional change for defense-related genes, and gene ontology (GO) enrichment analysis of RNAseq data revealed that a mixture of three oligosaccharide (oligo-mix) effectively activate the plants disease resistance. In practice, treatment of the oligo-mix enhanced the resistance of tomato to powdery mildew, but plant growth was not inhibited but rather tended to be promoted, providing evidence that mixed oligosaccharides have beneficial effects on improving disease resistance in plants, making them a promising class of compounds for practical application.

plant biology↗

bioRxiv2023

Disruption of maternal ACKR3 has profound effects on embryos and offspring.

ACKR3, scavenges and degrades the stem cell recruiting chemokine CXCL12 which is essential for proper embryonic, and in particular hematopoietic, development. Here we demonstrate strong expression of ACKR3 on trophoblasts. Using a pharmacological blocker we demonstrate that ACKR3 is essential for preventing movement of CXCL12 from the mother to the embryo with elevated plasma CXCL12 levels being detected in embryos from ACKR3-blocker treated mothers. Mice born to mothers treated with the blocker are lighter and shorter than those born to vehicle-treated mothers and, in addition, display profound anaemia associated with a markedly reduced bone marrow hematopoietic stem cell population. Importantly, whilst the hematopoietic abnormalities are corrected as mice age, our studies reveal a postnatal window during which offspring of ACKR3 blocker treated mice are unable to mount effective inflammatory responses to inflammatory/infectious stimuli. Overall, these data demonstrate that ACKR3 is essential for preventing CXCL12 transfer from mother to embryo and for ensuring properly regulated CXCL12 control over the development of the hematopoietic system.

developmental biology↗

bioRxiv2020

Diverse myeloid cells are recruited to the developing and inflamed mammary gland

The immune system plays fundamental roles in the mammary gland, shaping developmental processes and controlling inflammation during infection and cancer. Here we reveal unanticipated heterogeneity in the myeloid cell compartment during development of virgin, pregnant and involuting mouse mammary glands, and in milk. We investigate the functional consequences of individual and compound chemokine receptor deficiency on cell recruitment. Diverse myeloid cell recruitment was also shown in models of sterile inflammation and bacterial infection. Strikingly, we have shown that inflammation and infection can alter the abundance of terminal end buds, a key developmental structure, within the pubertal mammary gland. This previously unknown effect of inflammatory burden during puberty could have important implications for understanding the control of pubertal timing.

immunology↗

bioRxiv2019

Chemokine receptors CCR1 and ACKR2 coordinate mammary gland development

Macrophages are key regulators of developmental processes, including those involved in mammary gland development. We previously demonstrated that the atypical chemokine receptor, ACKR2, contributes to control of ductal epithelial branching in the developing mammary gland by regulating macrophage dynamics. ACKR2 is a chemokine-scavenging receptor, which mediates its effects through collaboration with inflammatory chemokine receptors (iCCRs). Here we reveal that ACKR2, and the iCCR CCR1, reciprocally regulate branching morphogenesis in the mammary gland, whereby stromal ACKR2 modulates levels of the shared ligand CCL7 to control the movement of a key population of CCR1-expressing macrophages to the ductal epithelium. In addition estrogen, which is essential for ductal elongation during puberty, upregulates CCR1 expression on macrophages. The age at which girls develop breasts is decreasing, which raises the risk of diseases including breast cancer. This study presents a previously unknown mechanism controlling the rate of mammary gland development during puberty and highlights potential therapeutic targets. SummaryIn the mammary gland during puberty, availability of the chemokine CCL7 is controlled by a scavenging receptor ACKR2 and provides a key signal to macrophages which have the receptor CCR1. Together, this controls the timing of development.

immunology↗