{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:45:33Z","timestamp":1793832333111,"version":"4.6.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Muscularis Externa<\/jats:italic> Macrophages (<jats:italic>ME<\/jats:italic>-Macs) and enteric glial cells (EGCs) are closely associated cell types in the bowel wall, and important interactions are thought to occur between them during intestinal inflammation. They are involved in developing postoperative ileus (POI), an acute, surgery-induced inflammatory disorder triggered by IL-1 receptor type I (IL1R1)-signaling. In this study, we demonstrate that IL1R1-signaling in murine and human EGCs induces a reactive state, named enteric gliosis, characterized by a strong induction of distinct chemokines, cytokines, and the colony-stimulating factors 1 and 3. Ribosomal tagging revealed enteric gliosis as an early part of POI pathogenesis, and mice with an EGC-restricted IL1R1-deficiency failed to develop postoperative enteric gliosis, showed diminished immune cell infiltration, and were protected from POI. Furthermore, the IL1R1-deficiency in EGCs altered the surgery-induced glial activation state and reduced phagocytosis in macrophages, as well as their migration and accumulation around enteric ganglia. In patients, bowel surgery also induced IL-1-signaling, key molecules of enteric gliosis, and macrophage activation. Together, our data show that IL1R1-signaling triggers enteric gliosis, which results in <jats:italic>ME<\/jats:italic>-Mac activation and the development of POI. Intervention in this pathway might be a useful prophylactic strategy in preventing such motility disorders and gut inflammation.<\/jats:p>","DOI":"10.1038\/s42003-022-03772-4","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T15:06:01Z","timestamp":1660316761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["IL-1-dependent enteric gliosis guides intestinal inflammation and dysmotility and modulates macrophage function"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-2703","authenticated-orcid":false,"given":"Reiner","family":"Schneider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Leven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpashree","family":"Mallesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Bre\u00dfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvio","family":"Mazzotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9444-1461","authenticated-orcid":false,"given":"Paola","family":"Fadda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-9766","authenticated-orcid":false,"given":"Tim","family":"Glowka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim O.","family":"Vilz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Lingohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg C.","family":"Kalff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fievos L.","family":"Christofi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8632-7631","authenticated-orcid":false,"given":"Sven","family":"Wehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"3772_CR1","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1053\/gast.1999.0029900378","volume":"117","author":"J Kalff","year":"1999","unstructured":"Kalff, J. et al. Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus. Gastroenterology 117, 378\u2013387 (1999).","journal-title":"Gastroenterology"},{"key":"3772_CR2","doi-asserted-by":"publisher","first-page":"O1","DOI":"10.1111\/codi.13210","volume":"18","author":"AM Wolthuis","year":"2016","unstructured":"Wolthuis, A. M. et al. Incidence of prolonged postoperative ileus after colorectal surgery: a systematic review and meta-analysis. Colorectal Dis. 18, O1\u20139 (2016).","journal-title":"Colorectal Dis."},{"key":"3772_CR3","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.jamcollsurg.2009.09.028","volume":"210","author":"T Asgeirsson","year":"2010","unstructured":"Asgeirsson, T. et al. Postoperative ileus. it costs more than you expect. J. Am. Coll. Surg. 210, 228\u2013231 (2010).","journal-title":"J. Am. Coll. Surg."},{"key":"3772_CR4","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1111\/codi.13582","volume":"19","author":"EG Peters","year":"2017","unstructured":"Peters, E. G. et al. Relation between postoperative ileus and anastomotic leakage after colorectal resection: a post hoc analysis of a prospective randomized controlled trial. Colorectal Dis. 19, 667\u2013674 (2017).","journal-title":"Colorectal Dis."},{"key":"3772_CR5","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1136\/gut.2005.089615","volume":"56","author":"S Wehner","year":"2007","unstructured":"Wehner, S. et al. Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents. Gut 56, 176\u2013185 (2007).","journal-title":"Gut"},{"key":"3772_CR6","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1053\/j.gastro.2013.09.030","volume":"146","author":"B Stoffels","year":"2014","unstructured":"Stoffels, B. et al. Postoperative ileus involves interleukin-1 receptor signaling in enteric glia. Gastroenterology 146, 176\u201387.e1 (2014).","journal-title":"Gastroenterology"},{"key":"3772_CR7","doi-asserted-by":"publisher","first-page":"581111","DOI":"10.3389\/fimmu.2020.581111","volume":"11","author":"J Enderes","year":"2020","unstructured":"Enderes, J. et al. A population of radio-resistant macrophages in the deep myenteric plexus contributes to postoperative ileus via toll-like receptor 3 signaling. Front. Immunol. 11, 581111 (2020).","journal-title":"Front. Immunol."},{"key":"3772_CR8","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1136\/gutjnl-2013-304676","volume":"63","author":"G Matteoli","year":"2014","unstructured":"Matteoli, G. et al. A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut 63, 938\u2013948 (2014).","journal-title":"Gut"},{"key":"3772_CR9","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.immuni.2017.05.011","volume":"46","author":"BB Yoo","year":"2017","unstructured":"Yoo, B. B. & Mazmanian, S. K. The enteric network: interactions between the immune and nervous systems of the gut. Immunity 46, 910\u2013926 (2017).","journal-title":"Immunity"},{"key":"3772_CR10","doi-asserted-by":"publisher","unstructured":"Wang, H., Foong, J. P. P., Harris, N. L. & Bornstein, J. C. Enteric neuroimmune interactions coordinate intestinal responses in health and disease. Mucosal Immunol. https:\/\/doi.org\/10.1038\/s41385-021-00443-1 (2021).","DOI":"10.1038\/s41385-021-00443-1"},{"key":"3772_CR11","doi-asserted-by":"publisher","unstructured":"Seguella, L. & Gulbransen, B. D. Enteric glial biology, intercellular signalling and roles in gastrointestinal disease. Nat. Rev. Gastroenterol. Hepatol. https:\/\/doi.org\/10.1038\/s41575-021-00423-7 (2021).","DOI":"10.1038\/s41575-021-00423-7"},{"key":"3772_CR12","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1053\/j.gastro.2017.07.002","volume":"153","author":"M Rao","year":"2017","unstructured":"Rao, M. et al. Enteric glia regulate gastrointestinal motility but are not required for maintenance of the epithelium in mice. Gastroenterology 153, 1068\u20131081.e7 (2017).","journal-title":"Gastroenterology"},{"key":"3772_CR13","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1097\/MIB.0000000000000854","volume":"22","author":"A Li\u00f1\u00e1n-Rico","year":"2016","unstructured":"Li\u00f1\u00e1n-Rico, A. et al. Molecular signaling and dysfunction of the human reactive enteric glial cell phenotype: implications for GI infection, IBD, POI, neurological, motility, and GI disorders. Inflamm. Bowel Dis. 22, 1812\u20131834 (2016).","journal-title":"Inflamm. Bowel Dis."},{"key":"3772_CR14","doi-asserted-by":"publisher","first-page":"102863","DOI":"10.1016\/j.isci.2021.102863","volume":"24","author":"HJ Rosenberg","year":"2021","unstructured":"Rosenberg, H. J. & Rao, M. Enteric glia in homeostasis and disease: From fundamental biology to human pathology. iScience 24, 102863 (2021).","journal-title":"iScience"},{"key":"3772_CR15","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/S0092-8674(00)81571-8","volume":"93","author":"TG Bush","year":"1998","unstructured":"Bush, T. G. et al. Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93, 189\u2013201 (1998).","journal-title":"Cell"},{"key":"3772_CR16","doi-asserted-by":"publisher","first-page":"13306","DOI":"10.1073\/pnas.231474098","volume":"98","author":"A Cornet","year":"2001","unstructured":"Cornet, A. et al. Enterocolitis induced by autoimmune targeting of enteric glial cells. a possible mechanism in Crohn\u2019s disease? Proc. Natl Acad. Sci. USA 98, 13306\u201313311 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3772_CR17","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1053\/j.gastro.2018.06.050","volume":"155","author":"BD Gulbransen","year":"2018","unstructured":"Gulbransen, B. D. & Christofi, F. L. Are we close to targeting enteric glia in gastrointestinal diseases and motility disorders? Gastroenterology 155, 245\u2013251 (2018).","journal-title":"Gastroenterology"},{"key":"3772_CR18","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.neuron.2014.12.037","volume":"85","author":"PS Kabouridis","year":"2015","unstructured":"Kabouridis, P. S. et al. Microbiota controls the homeostasis of glial cells in the gut lamina propria. Neuron 85, 289\u2013295 (2015).","journal-title":"Neuron"},{"key":"3772_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01165-z","volume":"9","author":"FA Vicentini","year":"2021","unstructured":"Vicentini, F. A. et al. Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia. Microbiome 9, 210 (2021).","journal-title":"Microbiome"},{"key":"3772_CR20","doi-asserted-by":"publisher","first-page":"e12724","DOI":"10.15252\/emmm.202012724","volume":"13","author":"R Schneider","year":"2021","unstructured":"Schneider, R. et al. A novel P2X2-dependent purinergic mechanism of enteric gliosis in intestinal inflammation. EMBO Mol. Med. 13, e12724 (2021).","journal-title":"EMBO Mol. Med."},{"key":"3772_CR21","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.neuron.2013.12.034","volume":"81","author":"JE Burda","year":"2014","unstructured":"Burda, J. E. & Sofroniew, M. V. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81, 229\u2013248 (2014).","journal-title":"Neuron"},{"key":"3772_CR22","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cell.2018.07.048","volume":"175","author":"SD Schepper","year":"2018","unstructured":"Schepper, S. D. et al. Self-maintaining gut macrophages are essential for intestinal homeostasis. Cell 175, 400\u2013415.e13 (2018).","journal-title":"Cell"},{"key":"3772_CR23","doi-asserted-by":"publisher","unstructured":"Rao, M. et al. Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system. Glia https:\/\/doi.org\/10.1002\/glia.22876 (2015).","DOI":"10.1002\/glia.22876"},{"key":"3772_CR24","doi-asserted-by":"publisher","first-page":"e0151335","DOI":"10.1371\/journal.pone.0151335","volume":"11","author":"C Rosenbaum","year":"2016","unstructured":"Rosenbaum, C. et al. Activation of myenteric glia during acute inflammation in vitro and in vivo. PLoS ONE 11, e0151335 (2016).","journal-title":"PLoS ONE"},{"key":"3772_CR25","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/j.celrep.2020.01.005","volume":"30","author":"U Brykczynska","year":"2020","unstructured":"Brykczynska, U. et al. Distinct transcriptional responses across tissue-resident macrophages to short-term and long-term metabolic challenge. Cell Rep. 30, 1627\u20131643.e7 (2020).","journal-title":"Cell Rep."},{"key":"3772_CR26","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1177\/1073858418783959","volume":"25","author":"MK Jha","year":"2019","unstructured":"Jha, M. K., Jo, M., Kim, J.-H. & Suk, K. Microglia-astrocyte crosstalk: an intimate molecular conversation. Neuroscientist 25, 227\u2013240 (2019).","journal-title":"Neuroscientist"},{"key":"3772_CR27","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.cell.2014.04.050","volume":"158","author":"PA Muller","year":"2014","unstructured":"Muller, P. A. et al. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158, 300\u2013313 (2014).","journal-title":"Cell"},{"key":"3772_CR28","doi-asserted-by":"publisher","first-page":"108100","DOI":"10.1016\/j.celrep.2020.108100","volume":"32","author":"V Grubi\u0161i\u0107","year":"2020","unstructured":"Grubi\u0161i\u0107, V. et al. Enteric glia modulate macrophage phenotype and visceral sensitivity following inflammation. Cell Rep. 32, 108100 (2020).","journal-title":"Cell Rep."},{"key":"3772_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46968-1","volume":"9","author":"KJ Hupa","year":"2019","unstructured":"Hupa, K. J. et al. AIM2 inflammasome-derived IL-1\u03b2 induces postoperative ileus in mice. Sci. Rep. 9, 10602 (2019).","journal-title":"Sci. Rep."},{"key":"3772_CR30","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.surg.2004.11.003","volume":"137","author":"S Wehner","year":"2005","unstructured":"Wehner, S. et al. Induction of IL-6 within the rodent intestinal muscularis after intestinal surgical stress. Surgery 137, 436\u2013446 (2005).","journal-title":"Surgery"},{"key":"3772_CR31","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1136\/gutjnl-2016-313144","volume":"66","author":"G Farro","year":"2017","unstructured":"Farro, G. et al. CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus. Gut 66, 2098\u20132109 (2017).","journal-title":"Gut"},{"key":"3772_CR32","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.3389\/fimmu.2018.02599","volume":"9","author":"K Stein","year":"2018","unstructured":"Stein, K. et al. Leukocyte-derived interleukin-10 aggravates postoperative ileus. Front. Immunol. 9, 2599 (2018).","journal-title":"Front. Immunol."},{"key":"3772_CR33","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.ebiom.2019.09.045","volume":"49","author":"S Val\u00e8s","year":"2019","unstructured":"Val\u00e8s, S. et al. Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesis. EBioMedicine 49, 172\u2013188 (2019).","journal-title":"EBioMedicine"},{"key":"3772_CR34","doi-asserted-by":"publisher","unstructured":"Leven, P., Schneider, R., Siemens, K., Jackson, W., & Wehner, S. Application of a RiboTag based approach to generate and analyze mRNA from enteric neural cells. Neurogastroenterol. Motility https:\/\/doi.org\/10.1111\/nmo.14309 (2021).","DOI":"10.1111\/nmo.14309"},{"key":"3772_CR35","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41586-021-04006-z","volume":"599","author":"F Progatzky","year":"2021","unstructured":"Progatzky, F. et al. Regulation of intestinal immunity and tissue repair by enteric glia. Nature 599, 125\u2013130 (2021).","journal-title":"Nature"},{"key":"3772_CR36","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jcmgh.2018.05.009","volume":"6","author":"NM Delvalle","year":"2018","unstructured":"Delvalle, N. M. et al. Communication between enteric neurons, glia, and nociceptors underlies the effects of tachykinins on neuroinflammation. Cell. Mol. Gastroenterol. Hepatol. 6, 321\u2013344 (2018).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"3772_CR37","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s00424-017-1948-4","volume":"469","author":"S Wehner","year":"2017","unstructured":"Wehner, S. & Engel, D. R. Resident macrophages in the healthy and inflamed intestinal muscularis externa. Pfl\u00fcgers Arch. Eur. J. Physiol. 469, 541\u2013552 (2017).","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"3772_CR38","doi-asserted-by":"publisher","first-page":"e13286","DOI":"10.1111\/nmo.13286","volume":"30","author":"S-S Lin","year":"2018","unstructured":"Lin, S.-S. et al. Alterations in the gut barrier and involvement of Toll-like receptor 4 in murine postoperative ileus. Neurogastroenterol. Motil. 30, e13286 (2018).","journal-title":"Neurogastroenterol. Motil."},{"key":"3772_CR39","doi-asserted-by":"publisher","unstructured":"Sommer, N. P., Schneider, R., Wehner, S., Kalff, J. C. & Vilz, T. O. State-of-the-art colorectal disease: postoperative ileus. Int. J. Colorectal Dis. https:\/\/doi.org\/10.1007\/s00384-021-03939-1 (2021).","DOI":"10.1007\/s00384-021-03939-1"},{"key":"3772_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-53414-9","volume":"9","author":"T Hyv\u00e4rinen","year":"2019","unstructured":"Hyv\u00e4rinen, T. et al. Co-stimulation with IL-1\u03b2 and TNF-\u03b1 induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system. Sci. Rep. 9, 1\u201315 (2019).","journal-title":"Sci. Rep."},{"key":"3772_CR41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jchemneu.2004.10.001","volume":"29","author":"AM Mu\u00f1oz","year":"2005","unstructured":"Mu\u00f1oz, A. M., Rey, P., Parga, J., Guerra, M. J. & Labandeira-Garcia, J. L. Glial overexpression of heme oxygenase-1: a histochemical marker for early stages of striatal damage. J. Chem. Neuroanat. 29, 113\u2013126 (2005).","journal-title":"J. Chem. Neuroanat."},{"key":"3772_CR42","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1179\/1743132810Y.0000000020","volume":"33","author":"HC Andersson","year":"2011","unstructured":"Andersson, H. C. et al. Trauma-induced reactive gliosis is reduced after treatment with octanol and carbenoxolone. Neurological Res. 33, 614\u2013624 (2011).","journal-title":"Neurological Res."},{"key":"3772_CR43","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1097\/00000658-199811000-00004","volume":"228","author":"JC Kalff","year":"1998","unstructured":"Kalff, J. C., Schraut, W. H., Simmons, R. L. & Bauer, A. J. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann. Surg. 228, 652\u2013663 (1998).","journal-title":"Ann. Surg."},{"key":"3772_CR44","doi-asserted-by":"publisher","first-page":"14303","DOI":"10.1073\/pnas.202332999","volume":"99","author":"L van Wesenbeeck","year":"2002","unstructured":"van Wesenbeeck, L. et al. The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene. Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification. Proc. Natl Acad. Sci. USA 99, 14303\u201314308 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3772_CR45","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cytogfr.2014.07.011","volume":"25","author":"LJ Bendall","year":"2014","unstructured":"Bendall, L. J. & Bradstock, K. F. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev. 25, 355\u2013367 (2014).","journal-title":"Cytokine Growth Factor Rev."},{"key":"3772_CR46","doi-asserted-by":"publisher","unstructured":"Pinheiro, D., Mawhin, M.-A., Prendecki, M. & Woollard, K. J. In-silico analysis of myeloid cells across the animal kingdom reveals neutrophil evolution by colony-stimulating factors. eLife 9, https:\/\/doi.org\/10.7554\/eLife.60214 (2020).","DOI":"10.7554\/eLife.60214"},{"key":"3772_CR47","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1038\/s41409-019-0449-9","volume":"54","author":"Q Wen","year":"2019","unstructured":"Wen, Q. et al. G-CSF-induced macrophage polarization and mobilization may prevent acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 54, 1419\u20131433 (2019).","journal-title":"Bone Marrow Transplant."},{"key":"3772_CR48","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cyto.2015.11.025","volume":"78","author":"S Meshkibaf","year":"2016","unstructured":"Meshkibaf, S., Martins, A. J., Henry, G. T. & Kim, S. O. Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages. Cytokine 78, 69\u201378 (2016).","journal-title":"Cytokine"},{"key":"3772_CR49","doi-asserted-by":"publisher","first-page":"e1115177","DOI":"10.1080\/2162402X.2015.1115177","volume":"5","author":"M Hollm\u00e9n","year":"2016","unstructured":"Hollm\u00e9n, M. et al. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer. Oncoimmunology 5, e1115177 (2016).","journal-title":"Oncoimmunology"},{"key":"3772_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2733-4","volume":"11","author":"H Fu","year":"2020","unstructured":"Fu, H. et al. Depletion of microglia exacerbates injury and impairs function recovery after spinal cord injury in mice. Cell Death Dis. 11, 528 (2020).","journal-title":"Cell Death Dis."},{"key":"3772_CR51","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1073\/pnas.1520398113","volume":"113","author":"N Lou","year":"2016","unstructured":"Lou, N. et al. Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier. Proc. Natl Acad. Sci. USA 113, 1074\u20131079 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3772_CR52","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nrneurol.2017.13","volume":"13","author":"DW Simon","year":"2017","unstructured":"Simon, D. W. et al. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat. Rev. Neurol. 13, 171\u2013191 (2017).","journal-title":"Nat. Rev. Neurol."},{"key":"3772_CR53","doi-asserted-by":"publisher","first-page":"E3709","DOI":"10.1073\/pnas.1619406114","volume":"114","author":"S Kulkarni","year":"2017","unstructured":"Kulkarni, S. et al. Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Proc. Natl Acad. Sci. USA 114, E3709\u201318 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3772_CR54","doi-asserted-by":"publisher","first-page":"5715","DOI":"10.1016\/j.cell.2021.10.004","volume":"184","author":"T Ahrends","year":"2021","unstructured":"Ahrends, T. et al. Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections. Cell 184, 5715\u20135727.e12 (2021).","journal-title":"Cell"},{"key":"3772_CR55","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jcmgh.2015.08.007","volume":"2","author":"IAM Brown","year":"2016","unstructured":"Brown, I. A. M., McClain, J. L., Watson, R. E., Patel, B. A. & Gulbransen, B. D. Enteric glia mediate neuron death in colitis through purinergic pathways that require connexin-43 and nitric oxide. Cell. Mol. Gastroenterol. Hepatol. 2, 77\u201391 (2016).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"3772_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36878-z","volume":"9","author":"DVS Costa","year":"2019","unstructured":"Costa, D. V. S. et al. 5-fluorouracil induces enteric neuron death and glial activation during intestinal mucositis via a S100B-RAGE-NF\u03baB-dependent pathway. Sci. Rep. 9, 665 (2019).","journal-title":"Sci. Rep."},{"key":"3772_CR57","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1136\/gut.2005.067595","volume":"55","author":"AC Aube","year":"2006","unstructured":"Aube, A. C. et al. Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption. Gut 55, 630\u2013637 (2006).","journal-title":"Gut"},{"key":"3772_CR58","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1053\/j.gastro.2008.12.058","volume":"136","author":"BD Gulbransen","year":"2009","unstructured":"Gulbransen, B. D. & Sharkey, K. A. Purinergic neuron-to-glia signaling in the enteric nervous system. Gastroenterology 136, 1349\u20131358 (2009).","journal-title":"Gastroenterology"},{"key":"3772_CR59","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1136\/gutjnl-2017-313856","volume":"66","author":"JM Pohl","year":"2017","unstructured":"Pohl, J. M. et al. Irf4-dependent CD103(+)CD11b(+) dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus. Gut 66, 2110\u20132120 (2017).","journal-title":"Gut"},{"key":"3772_CR60","doi-asserted-by":"publisher","first-page":"583422","DOI":"10.3389\/fphar.2020.583422","volume":"11","author":"E Mazzotta","year":"2020","unstructured":"Mazzotta, E., Villalobos-Hernandez, E. C., Fiorda-Diaz, J., Harzman, A. & Christofi, F. L. Postoperative ileus and postoperative gastrointestinal tract dysfunction: pathogenic mechanisms and novel treatment strategies beyond colorectal enhanced recovery after surgery protocols. Front. Pharmacol. 11, 583422 (2020).","journal-title":"Front. Pharmacol."},{"key":"3772_CR61","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923\u2013930 (2014).","journal-title":"Bioinformatics"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03772-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03772-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03772-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T09:05:41Z","timestamp":1669367141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03772-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,12]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3772"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03772-4","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,12]]},"assertion":[{"value":"23 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: S.W. and J.C.K. receive royalties from Wolter Kluwer for contributing to the postoperative ileus section of the <i>UpToDate<\/i> library. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"811"}}