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bioRxiv · 10.1101/2025.05.20.655028

Basophils activate splenic B cells and Dendritic cells via IL-13 signaling in acute Traumatic Brain Injury

olde Heuvel, F.·Zhang, J.·Sun, F.·Krishnamurthy, S. S.·Yartas, G.·Pagliarini, M.·Schaefer, M.·Huber-Lang, M.·Roselli, F.
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Abstract

Peripheral consequences following traumatic brain injury (TBI) are characterized by both systemic inflammatory responses and autonomic dysregulation, with almost all peripheral organs affected. One of the main immune regulatory organs, the spleen, shows high interaction with the brain which is controlled by both circulating mediators as well as autonomic fibers targeting splenic immune cells. The brain-spleen axis does not function as a one-way street, it also shows reciprocal effects where the spleen affects neuroinflammatory and cognitive functions post injury. To date, systemic and splenic inflammatory responses are measured by cells or mediators located in circulation. Nevertheless, most of the signaling and inflammation post injury takes place in the organs. Therefore, we set out to investigate the early signaling landscape in the spleen following TBI, using phospho-proteomic signaling approaches and immunofluorescence stainings to investigate novel molecular and cellular players. Based on the signaling signature, we found a rapid influx of basophil granulocytes towards the spleen, which are recruited via CXCL1 expressed by B-cells and dendritic cells. The basophils activate B cells and dendritic cells (DCs) via the IL-13/IL-13Ra1 signaling pathway to enhance protein translation through the long non-coding RNA NORAD. The early recruitment of basophils and subsequent activation of B cells and DCs, is short lived and sets at 3dpi. Interestingly, the rapid recruitment of basophils is inhibited by ethanol intoxication in TBI. In conclusion, basophils recruitment to the spleen may serve as an early mediator of systemic inflammatory responses to TBI with potential implications for research on biomarkers and therapeutic targets.

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olde Heuvel, F., Zhang, J., Sun, F., Krishnamurthy, S. S., Yartas, G., Pagliarini, M., Schaefer, M., Huber-Lang, M., Roselli, F.. 2025-05-21. Basophils activate splenic B cells and Dendritic cells via IL-13 signaling in acute Traumatic Brain Injury. https://doi.org/10.1101/2025.05.20.655028

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