Table_1_Gcm counteracts Toll-induced inflammation and impacts hemocyte number through cholinergic signaling.xlsx

Hemocytes, the myeloid-like immune cells of Drosophila, fulfill 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 Glial cell deficient/Glial cell missing (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 reactive oxygen species (ROS) signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. In addition, our data reveal the expression of acetylcholine 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 nicotinic acetylcholine receptor alpha 6 (nAchRalpha6) regulating hemocyte proliferation in a cell autonomous fashion and for non-cell autonomous cholinergic signaling regulating the number of hemocytes. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response.

血细胞（hemocytes）作为果蝇的髓系样免疫细胞，承担着多种尚未完全阐明的功能，涵盖吞噬作用至炎症信号转导等多个领域。本研究证实，下调血细胞特异性的胶质细胞缺陷/胶质细胞缺失（Glide/Gcm）转录因子的表达，可增强机体针对Toll通路（Toll pathway）组成型激活的炎症应答。该现象与谷胱甘肽S-转移酶（glutathione S-transferase）水平降低相关，提示Glide/Gcm参与活性氧（reactive oxygen species, ROS）信号通路，并暗示其具备广泛的抗炎潜能。此外，本研究数据揭示了乙酰胆碱受体在血细胞中的表达，且Toll通路激活会影响其表达水平，这一发现揭示了由神经递质介导的炎症应答的全新维度。最后，本研究证实烟碱型乙酰胆碱受体α6（nAchRalpha6）可通过细胞自主方式调控血细胞增殖，而非细胞自主的胆碱能信号通路则可影响血细胞数量。综上，本研究为炎症应答相关的分子通路提供了全新的认知。