Enteric glial cells favor accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation

作者：Michelle Stakenborg, Saeed Abdurahiman, Veronica De Simone, Gera Goverse, Nathalie Stakenborg, Lies van Baarle, Qin Wu, Dimitri Pirottin, Jung‐Seok Kim, Louise Chappell‐Maor, Isabel Pintelon, Sofie Thys, Emilie Pollenus, Louis Boon, Philippe E. Van den Steen, Marlene M. Hao, Jo A. Van Ginderachter, Guy E. Boeckxstaens, Jean‐Pierre Timmermans, Steffen Jung, Thomas Marichal, Sales Ibiza, Gianluca Matteoli · 发表于：Mucosal Immunology · 年份：2022 · DOI：10.1038/s41385-022-00563-2 · 被引用次数：58 · 研究领域：Immune cells in cancer、Neuroinflammation and Neurodegeneration Mechanisms、Immune Cell Function and Interaction

Monocyte-derived macrophages (Mϕs) are crucial regulators during muscularis inflammation. However, it is unclear which micro-environmental factors are responsible for monocyte recruitment and anti-inflammatory Mϕ differentiation in this paradigm. Here, we investigate Mϕ heterogeneity at different stages of muscularis inflammation and determine how environmental cues can attract and activate tissue-protective Mϕs. Results showed that muscularis inflammation induced marked alterations in mononuclear phagocyte populations associated with a rapid infiltration of Ly6c + monocytes that locally acquired unique transcriptional states. Trajectory inference analysis revealed two main pro-resolving Mϕ subpopulations during the resolution of muscularis inflammation, i.e. Cd206 + MhcII hi and Timp2 + MhcII lo Mϕs. Interestingly, we found that damage to the micro-environment upon muscularis inflammation resulted in EGC activation, which in turn stimulated monocyte infiltration and the consequent differentiation in anti-inflammatory CD206 + Mϕs via CCL2 and CSF1, respectively. In addition, CSF1-CSF1R signaling was shown to be essential for the differentiation of monocytes into CD206 + Mϕs and EGC proliferation during muscularis inflammation. Our study provides a comprehensive insight into pro-resolving Mϕ differentiation and their regulators during muscularis inflammation. We deepened our understanding in the interaction between EGCs and Mϕs, thereby highlighting pro-resolving Mϕ differenti...