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SFRP1 modulates astrocyte‐to‐microglia crosstalk in acute and chronic neuroinflammation
Author(s) -
RuedaCarrasco Javier,
MartinBermejo María Jesús,
Pereyra Guadalupe,
Mateo María Inés,
Borroto Aldo,
Brosseron Frederic,
Kummer Markus P,
Schwartz Stephanie,
LópezAtalaya José P,
Alarcon Balbino,
Esteve Pilar,
Heneka Michael T,
Bovolenta Paola
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051696
Subject(s) - neuroinflammation , microglia , astrocyte , crosstalk , neuroscience , inflammation , biology , downregulation and upregulation , microbiology and biotechnology , immunology , central nervous system , gene , biochemistry , physics , optics
Neuroinflammation is a common feature of many neurodegenerative diseases. It fosters a dysfunctional neuron–microglia–astrocyte crosstalk that, in turn, maintains microglial cells in a perniciously reactive state that often enhances neuronal damage. The molecular components that mediate this critical communication are not fully explored. Here, we show that secreted frizzled‐related protein 1 (SFRP1), a multifunctional regulator of cell‐to‐cell communication, is part of the cellular crosstalk underlying neuroinflammation. In mouse models of acute and chronic neuroinflammation, SFRP1, largely astrocyte‐derived, promotes and sustains microglial activation, and thus a chronic inflammatory state. SFRP1 promotes the upregulation of components of the hypoxia‐induced factor‐dependent inflammatory pathway and, to a lower extent, of those downstream of the nuclear factor‐kappa B. We thus propose that SFRP1 acts as an astrocyte‐to‐microglia amplifier of neuroinflammation, representing a potential valuable therapeutic target for counteracting the harmful effect of chronic inflammation in several neurodegenerative diseases.