{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:07:58Z","timestamp":1780096078704,"version":"3.54.0"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T00:00:00Z","timestamp":1624665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WE4204\/3-1"],"award-info":[{"award-number":["WE4204\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interactions between the peripheral nervous system and resident macrophages (MMs) modulate intestinal homeostatic functions. Activation of \u03b22-adrenergic receptors on MMs has been shown to reduce bacterial challenges. These MMs are also crucial for the development of bowel inflammation in postoperative ileus (POI), an iatrogenic, noninfectious inflammation-based motility disorder. However, the role of the sympathetic nervous system (SNS) in the immune modulation of these MMs during POI or other noninfectious diseases is largely unknown. By employing 6-OHDA-induced denervation, we investigated the changes in the muscularis externa by RNA-seq, quantitative PCR, and flow cytometry. Further, we performed transcriptional phenotyping of sorted CX3CR1+ MMs and ex vivo LPS\/M-CSF stimulation on these MMs. By combining denervation with a mouse POI model, we explored distinct changes on CX3CR1+ MMs as well as in the muscularis externa and their functional outcome during POI. Our results identify SNS as an important mediator in noninfectious postoperative inflammation. Upon denervation, MMs anti-inflammatory genes were reduced, and the muscularis externa profile is shaped toward a proinflammatory status. Further, denervation reduced MMs anti-inflammatory genes also in the early phase of POI. Finally, reduced leukocyte infiltration into the muscularis led to a quicker recovery of bowel motility in the late phase of POI.<\/jats:p>","DOI":"10.3390\/ijms22136872","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T22:24:57Z","timestamp":1624832697000},"page":"6872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sympathetic Denervation Alters the Inflammatory Response of Resident Muscularis Macrophages upon Surgical Trauma and Ameliorates Postoperative Ileus in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4402-8964","authenticated-orcid":false,"given":"Shilpashree","family":"Mallesh","sequence":"first","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-2703","authenticated-orcid":false,"given":"Reiner","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Schneiker","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Lysson","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Efferz","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins, Krieger School of Arts and Sciences, Baltimore, MD 3400, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter J","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"},{"name":"Tytgat Institute of Liver and Intestinal Research, Academic Medical Center, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8632-7631","authenticated-orcid":false,"given":"Sven","family":"Wehner","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/35013070","article-title":"Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin","volume":"405","author":"Borovikova","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"418","DOI":"10.3389\/fnins.2019.00418","article-title":"Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation","volume":"13","author":"Payne","year":"2019","journal-title":"Front. 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