TY  - JOUR
AU  - Kovacs, Daniel
AU  - Heger, Klaus
AU  - Giansanti, Piero
AU  - Iuliano, Caterina
AU  - Meissner, Felix
AU  - Mann, Matthias
AU  - Böttcher, Jan
AU  - Öllinger, Ruppert
AU  - Rad, Roland
AU  - Tammer, Freya
AU  - Gölling, Vanessa
AU  - Zeng, Theodor
AU  - Masjedi, Ali
AU  - Dr Med Vet, Tanja Groll
AU  - Roers, Axel
AU  - Babina, Magda
AU  - Robles, Maria S
AU  - Moser, Markus
AU  - Kaesler, Susanne
AU  - Dr Med Vet, Katja Steiger
AU  - Biedermann, Tilo
AU  - Schmidt-Supprian, Marc
TI  - Mast cells modulate macrophage biology through release of pre-stored CSF1.
JO  - The journal of allergy and clinical immunology
VL  - nn
SN  - 0091-6749
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2025-01183
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.
KW  - CSF1 (Other)
KW  - mast cell (Other)
KW  - mast cell mediator (Other)
KW  - melanoma (Other)
KW  - proteome (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40480612
DO  - DOI:10.1016/j.jaci.2025.05.022
UR  - https://inrepo02.dkfz.de/record/301913
ER  -