TY - JOUR
T1 - Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance
AU - Braza, Mounia S.
AU - Conde, Patricia
AU - Garcia, Mercedes
AU - Cortegano, Isabel
AU - Brahmachary, Manisha
AU - Pothula, Venu
AU - Fay, Francois
AU - Boros, Peter
AU - Werner, Sherry A.
AU - Ginhoux, Florent
AU - Mulder, Willem J. M.
AU - Ochando, Jordi
PY - 2018
Y1 - 2018
N2 - The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.
AB - The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85041640240&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29314558
U2 - https://doi.org/10.1111/ajt.14645
DO - https://doi.org/10.1111/ajt.14645
M3 - Article
C2 - 29314558
SN - 1600-6135
VL - 18
SP - 1247
EP - 1255
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 5
ER -