Riet, C. | Search bioRxiv

bioRxiv2023

Gcm alleviates the inflammatory phenotype induced by Toll activation in Drosophila hemocytes

Hemocytes, the myeloid-like immune cells of Drosophila, fulfil a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glide/Gcm transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S transferase, suggesting an implication of Glide/Gcm in ROS signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. We show the expression of neurotransmitter receptors in hemocytes and that Toll activation affects their expressions, disclosing a novel aspect of the inflammatory response mediated by neurotransmitters. Finally, we provide evidence for acetylcholine receptor nAchRalpha6 regulating hemocyte proliferation. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response.

immunology↗

bioRxiv2022

Gcm: a novel anti-inflammatory transcriptional cascade conserved from flies to humans

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.

neuroscience↗