TY - JOUR
T1 - Enteric glial cells favor accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation
AU - Stakenborg, Michelle
AU - Abdurahiman, Saeed
AU - De Simone, Veronica
AU - Goverse, Gera
AU - Stakenborg, Nathalie
AU - van Baarle, Lies
AU - Wu, Qin
AU - Pirottin, Dimitri
AU - Kim, Jung-Seok
AU - Chappell-Maor, Louise
AU - Pintelon, Isabel
AU - Thys, Sofie
AU - Pollenus, Emilie
AU - Boon, Louis
AU - Van den Steen, Philippe
AU - Hao, Marlene
AU - Van Ginderachter, Jo A
AU - Boeckxstaens, Guy E
AU - Timmermans, Jean-Pierre
AU - Jung, Steffen
AU - Marichal, Thomas
AU - Ibiza, Sales
AU - Matteoli, Gianluca
PY - 2022/9/7
Y1 - 2022/9/7
N2 - 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+ MhcIIhi and Timp2+ MhcIIlo 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 differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.
AB - 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+ MhcIIhi and Timp2+ MhcIIlo 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 differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.
U2 - 10.1038/s41385-022-00563-2
DO - 10.1038/s41385-022-00563-2
M3 - Article
SN - 1933-0219
JO - Mucosal Immunology
JF - Mucosal Immunology
ER -