title: The complex STATes of astrocyte reactivity: How are they controlled by the JAK-STAT3 pathway?
abstract: Astrocytes play multiple important roles in brain physiology. In pathological conditions, they become reactive, which is characterized by morphological changes and upregulation of intermediate filament proteins. Besides these descriptive hallmarks, astrocyte reactivity involves significant transcriptional and functional changes that are far from being fully understood. Most importantly, astrocyte reactivity seems to encompass multiple states, each having a specific influence on surrounding cells and disease progression. These diverse functional states of reactivity must be regulated by subtle signaling networks. Many signaling cascades have been associated with astrocyte reactivity, but among them, the JAK-STAT3 pathway is emerging as a central regulator. In this review, we aim (i) to show that the JAK-STAT3 pathway plays a key role in the control of astrocyte reactivity, (ii) to illustrate that STAT3 is a pleiotropic molecule operating multiple functions in reactive astrocytes, and (iii) to suggest that each specific functional state of reactivity is governed by complex molecular interactions within astrocytes, which converge on STAT3. More research is needed to precisely identify the signaling networks controlling the diverse states of astrocyte reactivity. Only then, we will be able to precisely delineate the therapeutic potential of reactive astrocytes in each neurological disease context.
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut d'Imagerie Biomédicale (I2BM), MIRCen, F-92260 Fontenay-aux-Roses, France; Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, Neurodegenerative Diseases Laboratory, F-92260 Fontenay-aux-Roses, France. Electronic address: Kelly.ceyzeriat@cea.fr.
authors.forename: Kelly
authors.initials: K
authors.lastname: Ceyzériat
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut d'Imagerie Biomédicale (I2BM), MIRCen, F-92260 Fontenay-aux-Roses, France; Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, Neurodegenerative Diseases Laboratory, F-92260 Fontenay-aux-Roses, France. Electronic address: Laurene.abjean@cea.fr.
authors.forename: Laurene
authors.initials: L
authors.lastname: Abjean
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut d'Imagerie Biomédicale (I2BM), MIRCen, F-92260 Fontenay-aux-Roses, France; Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, Neurodegenerative Diseases Laboratory, F-92260 Fontenay-aux-Roses, France. Electronic address: maria.carrillo@cea.fr.
authors.forename: María-Angeles
authors.initials: MA
authors.lastname: Carrillo-de Sauvage
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut d'Imagerie Biomédicale (I2BM), MIRCen, F-92260 Fontenay-aux-Roses, France; Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, Neurodegenerative Diseases Laboratory, F-92260 Fontenay-aux-Roses, France; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, CA 94143, USA. Electronic address: Lucile.BenHaim@ucsf.edu.
authors.forename: Lucile
authors.initials: L
authors.lastname: Ben Haim
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut d'Imagerie Biomédicale (I2BM), MIRCen, F-92260 Fontenay-aux-Roses, France; Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, Neurodegenerative Diseases Laboratory, F-92260 Fontenay-aux-Roses, France. Electronic address: carole.escartin@cea.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Escartin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050796:STAT3 Transcription Factor; D053612:Janus Kinases
keywords: JAK–STAT pathway; STAT3; neurological diseases; reactive astrocytes; signaling cascades