Cover Image

Mast cells modulate macrophage biology through release of prestored CSF1

Background - Mast cells (MCs) 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 granul...

Full description

Saved in:
Bibliographic Details
Main Authors: Kovács, Dániel (Author) , Heger, Klaus (Author) , Giansanti, Piero (Author) , Iuliano, Caterina (Author) , Meissner, Felix (Author) , Mann, Matthias (Author) , Böttcher, Jan (Author) , Öllinger, Ruppert (Author) , Rad, Roland (Author) , Tammer, Freya (Author) , Gölling, Vanessa (Author) , Zeng, Theodor (Author) , Masjedi, Ali (Author) , Groll, Tanja (Author) , Roers, Axel (Author) , Babina, Magda (Author) , Robles, Maria S. (Author) , Moser, Markus (Author) , Kaesler, Susanne (Author) , Steiger, Katja (Author) , Biedermann, Tilo (Author) , Schmidt-Supprian, Marc (Author)
Format: Article (Journal)
Language:English
Published: 5 November 2025
In: The journal of allergy and clinical immunology
Year: 2025, Volume: 156, Issue: 5, Pages: 1260-1276
ISSN:1097-6825
DOI:10.1016/j.jaci.2025.05.022
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jaci.2025.05.022
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0091674925006177
Get full text
Author Notes:Daniel Kovacs, MSc, Klaus Heger, PhD, Piero Giansanti, PhD, Caterina Iuliano, PhD, Felix Meissner, PhD, Matthias Mann, PhD, Jan Böttcher, PhD, Ruppert Öllinger, PhD, Roland Rad, MD, Freya Tammer, Vanessa Gölling, MSc, Theodor Zeng, MSc, Ali Masjedi, MSc, Tanja Groll, Dr med vet, Axel Roers, MD, Magda Babina, PhD, Maria S. Robles, PhD, Markus Moser, PhD, Susanne Kaesler, PhD, Katja Steiger, Dr med vet, Tilo Biedermann, MD, and Marc Schmidt-Supprian, PhD
Description
Summary:Background - Mast cells (MCs) 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. - Objective - We sought to systematically and globally identify MC-released protein mediators and elucidate their functions. - Methods - We analyzed the secretomes of antigen-activated primary mouse MCs using quantitative mass spectrometry-based proteomics and conducted follow-up studies in vitro, ex vivo, and using MC-specific genetic mouse models. - Results - We identified CSF1 as a novel preformed MC mediator present in the granules of all connective tissue MCs. We further show that the MC secretome can induce macrophage differentiation and a unique polarization pattern via CSF1 and other mediators. MC-derived CSF1 has systemic functions, because MC-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 MC-derived CSF1 promotes cancer cell expansion. Finally, we demonstrate that CSF1 is also prestored and released by human MCs. - Conclusions - CSF1 is an evolutionarily conserved, constitutive MC granule component. MC degranulation induces macrophage differentiation and a unique polarization state, the former being completely dependent on CSF1, whereas the latter is only modulated.
Item Description:Online verfügbar 4 June 2025, Version des Artikels 5 November 2025
Gesehen am 09.03.2026
Physical Description:Online Resource
ISSN:1097-6825
DOI:10.1016/j.jaci.2025.05.022

Similar Items