Daglas, M. | Search bioRxiv

bioRxiv2026

Immune responses to infection modulate peripheral sympathetic neuron functions

The central nervous system interprets inflammatory signals in the body and directs the modulation of inflammatory responses by reflexively engaging peripheral sympathetic neurons1,2. This includes sympathetic neurons that innervate the spleen, which can regulate immune functions3-5 and modulate inflammation6-8. Yet, it is unclear if neuroimmune interactions involve specialised immunoregulatory sympathetic neurons, and if the immune system can reciprocally regulate peripheral sympathetic neurons to control these responses. Using retrograde tracing and single-cell transcriptomics, we find that spleen-innervating neurons are heterogeneous but do not exhibit a distinct transcriptional program indicative of specialisation for immune communication. However, we report that immune responses induced by pathogens can regulate postganglionic sympathetic neuron functions. Cytokines produced by immune cells downregulate expression of the neurotrophin nerve growth factor in spleen mesenchymal cells, leading to organ-specific sympathetic nerve retraction from the spleen. Concurrently, splenic type I interferon signalling induces inflammatory gene expression in neurons and suppresses neuron excitability. Chemogenetic activation of sympathetic neurons demonstrates an impaired anti-inflammatory capacity in the spleen during infection. These results reveal regulation of sympathetic neuronal functions by the immune system, which could support optimal generation of immune responses against pathogens.

immunology↗

bioRxiv2025

A multi-scale vascular atlas of blood vessels within the urinary bladder of male and female mice

The vascular supply of the urinary bladder is embedded within a highly dynamic environment that includes alternating cycles of regional compression or stretching during bladder filling, sustained continence and voiding. These place unique demands on the vasculature to maintain tissue perfusion, fluid homeostasis and immune surveillance. Understanding this vascular regulation is also highly relevant to defining mechanisms of organ reperfusion following pelvic surgery, pelvic venous insufficiency, and the impacts of diabetes and ischemia on urinary function. There is limited anatomical knowledge on the organization of this vascular network, so we aimed to determine if there are stereotypical features associated with the mouse urinary bladder. We applied advanced microscopy and anatomical visualization methods to samples of the entire bladder viewed as a whole mount, including intravital tomato lectin labeling of the arterial vasculature, multi-channel immunofluorescence, tissue clearing, light-sheet and confocal microscopy. We developed a comprehensive multi-scale 3D anatomical map of the stereotypical arterial and venous networks associated with the mouse urinary bladder in both sexes, showing that the primary features of this network are established by the early postnatal period, prior to maturation of voiding and continence reflexes. These outcomes provide the foundation for probing mechanisms that underpin physiological and pathophysiological changes in the urinary bladder vascular network and a resource to guide more refined experimental perturbation, analysis and interpretation of vascular function/dysfunction in mouse models. This new knowledge on the structure of the urinary bladder vascular network will also benefit tissue engineering efforts seeking to restore or replace this organ.

physiology↗