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@ARTICLE{OldeHeuvel:282965,
author = {Olde Heuvel, Florian and Zhang, Jin and Sun, Fan and
Krishnamurthy, Sruthi Sankari and Yartas, Gizem and Özkan,
Burak and Pagliarini, Marica and Voehringer, David and
O'Meara, Caitlin C and Schäfer, Michael K E and Huber-Lang,
Markus and Roselli, Francesco},
title = {{B}asophils activate splenic {B} cells and dendritic cells
via {IL}-13 signaling in acute traumatic brain injury.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
issn = {1742-2094},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2025-01417},
pages = {290},
year = {2025},
abstract = {Peripheral consequences following traumatic brain injury
(TBI) are characterized by both systemic inflammatory
responses and autonomic dysregulation. 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.We set
out to investigate the early (3 h) signaling landscape in
the spleen following a moderate severity closed head injury
model to wild-type animals aged p60-90. Using
phospho-proteomic signaling approaches, immunofluorescence
stainings, Enzyme-Linked Immunosorbent Assay (ELISA),
super-resolution microscopy and single mRNA in situ
hybridization we investigated novel molecular and cellular
players in the spleen involved in immune modulation after a
head injury.Based on the signaling signature, we found a
rapid influx of basophil granulocytes towards the spleen,
via a recruitment mechanism that includes CXCL1 expressed by
B-cells and dendritic cells (DCs). The basophils in turn
seem to activate B cells and dendritic cells via the
IL-13/IL-13Ra1 signaling pathway and 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, with a subsequent
prevention of IL-13Ra phosphorylation and NORAD increase in
B-cells and DCs.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.},
keywords = {Animals / Brain Injuries, Traumatic: immunology / Brain
Injuries, Traumatic: metabolism / Brain Injuries, Traumatic:
pathology / Mice / Spleen: immunology / Spleen: metabolism /
Spleen: pathology / Signal Transduction: physiology /
B-Lymphocytes: metabolism / B-Lymphocytes: immunology /
Interleukin-13: metabolism / Interleukin-13: immunology /
Basophils: metabolism / Basophils: immunology / Mice, Inbred
C57BL / Dendritic Cells: metabolism / Dendritic Cells:
immunology / Male / B-cell (Other) / Basophil (Other) /
Dendritic cell (Other) / IL-13 (Other) / Spleen (Other) /
Traumatic brain injury (Other) / Interleukin-13 (NLM
Chemicals)},
cin = {AG Roselli},
ddc = {610},
cid = {I:(DE-2719)1910001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41408561},
doi = {10.1186/s12974-025-03621-1},
url = {https://pub.dzne.de/record/282965},
}