Deczkowska, A. | Search bioRxiv

bioRxiv2025

Local B cell maturation and mast cell regulation of choroid plexus function in early life.

Postnatal development is a critical period for the maturation of the nervous and immune systems. The choroid plexus (CP) within the brain ventricles guides brain development through the production of cerebrospinal fluid and responds to stimuli from its local immune microenvironment. Here, using single-cell sequencing, we chart the establishment of the immune niche within the CP from birth to adulthood. We demonstrate that the CP is an active site for the development of B cells from early pro-B cells to mature B cells. We also characterize a transient population of CP mast cells that is highly abundant in the perinatal period. Single activation of these cells shortly after birth led to activation of serotonin-dependent secretion from the CP epithelial cells and resulted in cognitive impairment later in life. Our findings highlight the crucial nature of the CP as a neuroimmune interface, where cellular crosstalk regulates key functions of CP activity, thereby guiding brain development.

immunology↗

bioRxiv2025

Alzheimer's disease causes bone marrow myelopoiesis dysfunction

Accumulating evidence suggests that both innate and adaptive immunity play crucial roles in combating Alzheimers disease (AD). Specifically, enhancing the homing of monocyte-derived macrophages to the affected brain has been shown to reduce local inflammation, decrease proteinopathy, rescue neurons, and mitigate cognitive decline. However, the factors limiting their spontaneous recruitment remain unclear. Using multi-omics techniques, we identified impaired myelopoiesis and monocyte development in both mice and AD patients. While not the primary cause of the disease, this impairment is associated with disease progression. In the 5xFAD mouse model, monocyte differentiation was found to be disrupted due to a maladaptive bone marrow (BM) response, driven by type I interferon (IFN-I) signaling. A similar phenotype was found in circulating monocytes from AD patients compared to healthy controls. Blocking IFN-I with monoclonal antibodies or using chimeric AD mice with BM from mice lacking the IFN-I receptor (IFNAR1) alleviated myelopoiesis dysfunction, normalized monocyte phenotypes, and reduced cognitive impairment. These improvements in myeloid function were accompanied by an increased homing of monocyte-derived macrophages in the AD brain. Our results reveal an unexpected dysfunction in BM myelopoiesis in the context of neurodegeneration and support the emerging concept that neurodegenerative diseases are not solely brain-centric.

neuroscience↗