An anti-inflammatory transcriptional cascade conserved from flies to humans
Autor: | Alexia Pavlidaki, Radmila Panic, Sara Monticelli, Céline Riet, Yoshihiro Yuasa, Pierre B. Cattenoz, Brahim Nait-Oumesmar, Angela Giangrande |
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Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cattenoz, Pierre |
Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Inflammation
[SDV]Life Sciences [q-bio] aging Anti-Inflammatory Agents Lysophosphatidylcholines Cell Differentiation [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity immunity General Biochemistry Genetics and Molecular Biology DNA-Binding Proteins Mice neuro-inflammation [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] transcription factors [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Humans Animals Drosophila Proteins Drosophila [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity Aged |
Zdroj: | Cell Reports Cell Reports, 2022, 41 (3), pp.111506. ⟨10.1016/j.celrep.2022.111506⟩ |
ISSN: | 2211-1247 |
Popis: | International audience; Innate immunity is an ancestral process that can induce pro-and anti-inflammatory states. A major challenge is to characterise the transcriptional cascades that modulate the response to chronic and acute inflammatory challenges. The Drosophila melanogaster Gcm transcription factor represents an interesting candidate for its potential anti-inflammatory role. Here we explore its evolutionary conservation and its mode of action. We found that the murine ortholog Gcm2 (mGcm2) is expressed upon aging, which is considered as a state of chronic inflammation. mGcm2 is found in a subpopulation of microglia, the innate immune cells of the central nervous system (CNS). Its expression is also induced by a lyso-phosphatidylcholine (LPC)-induced CNS demyelination (acute inflammation) and mGcm2 conditional knock out mice show an increased inflammatory phenotype upon aging or LPC injection. In agreement with the role of this transcriptional cascade in inflammation, the human ortholog hGCM2 is expressed in active demyelinating lesions of Multiple Sclerosis (MS) patients. Finally, Drosophila gcm expression is induced upon aging as well as during an acute inflammatory response and its overexpression decreases the inflammatory phenotype. Altogether, our data show that the inducible Gcm pathway is highly conserved from flies up to humans and represents a potential therapeutic anti-inflammatory target in the control of the inflammatory response. |
Databáze: | OpenAIRE |
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