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@ARTICLE{Kovacs:301913,
author = {D. Kovacs and K. Heger and P. Giansanti and C. Iuliano and
F. Meissner and M. Mann and J. Böttcher and R. Öllinger
and R. Rad$^*$ and F. Tammer and V. Gölling and T. Zeng and
A. Masjedi and T. G. Dr Med Vet and A. Roers and M. Babina
and M. S. Robles and M. Moser and S. Kaesler and K. S. Dr
Med Vet and T. Biedermann and M. Schmidt-Supprian$^*$},
title = {{M}ast cells modulate macrophage biology through release of
pre-stored {CSF}1.},
journal = {The journal of allergy and clinical immunology},
volume = {nn},
issn = {0091-6749},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-01183},
pages = {nn},
year = {2025},
note = {epub},
abstract = {Mast cells are tissue-resident immune cells present in
connective tissues throughout the body. They exert diverse
functions in immunity by rapidly releasing a plethora of
preformed mediators, including proteoglycans, cytokines, and
proteases, which are stored in cytoplasmic granules.Our aim
was to systematically and globally identify mast
cell-released protein mediators and elucidate their
functions.We analysed the secretomes of antigen-activated
primary mouse mast cells using quantitative mass
spectrometry-based proteomics and conducted follow-up
studies in vitro, ex vivo and using mast cell-specific
genetic mouse models.We identified CSF1 as a novel preformed
mast cell mediator present in the granules of all connective
tissue-type mast cells. We further show that the mast cell
secretome can induce macrophage differentiation and a unique
polarisation pattern via CSF1 and other mediators. Mast
cell-derived CSF1 has systemic functions, as mast
cell-specific CSF1-deficient mice have lower serum CSF1
levels and reduced numbers of circulating monocytes. In
addition, using an orthotopic transplantation-based melanoma
mouse model, we show that loss of mast cell-derived CSF1
promotes cancer cell expansion. Finally, we demonstrate that
CSF1 is also prestored and released by human mast cells.CSF1
is an evolutionarily conserved, constitutive mast cell
granule component. Mast cell degranulation induces
macrophage differentiation and a unique polarisation state,
the former being completely dependent on CSF1, while the
latter is only modulated.},
keywords = {CSF1 (Other) / mast cell (Other) / mast cell mediator
(Other) / melanoma (Other) / proteome (Other)},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40480612},
doi = {10.1016/j.jaci.2025.05.022},
url = {https://inrepo02.dkfz.de/record/301913},
}