{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:24:57Z","timestamp":1784769897830,"version":"3.55.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["19K07908"],"award-info":[{"award-number":["19K07908"]}]},{"name":"JSPS KAKENHI","award":["18K06698"],"award-info":[{"award-number":["18K06698"]}]},{"name":"JSPS KAKENHI","award":["20K07098"],"award-info":[{"award-number":["20K07098"]}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","award":["2020T003"],"award-info":[{"award-number":["2020T003"]}],"id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Moonshot R&D","award":["JPMJMS2021"],"award-info":[{"award-number":["JPMJMS2021"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Several studies have demonstrated that \u03b17 nicotinic acetylcholine receptors (\u03b17nAChRs) exert anti-inflammatory effects on immune cells and nicotine suppress UC onset and relapse. Plasmacytoid dendritic cells (pDCs) reportedly accumulate in the colon of UC patients. Therefore, we investigated the pathophysiological roles of \u03b17nAChRs on pDCs in the pathology of UC using oxazolone (OXZ)-induced Th2-type colitis with BALB\/c mice. 2-deoxy-D-glucose, a central vagal stimulant suppressed OXZ colitis, and nicotine also ameliorated OXZ colitis with suppressing Th2 cytokines, which was reversed by \u03b17nAChR antagonist methyllycaconitine. Additionally, \u03b17nAChRs were expressed on pDCs, which were located very close to cholinergic nerve fibers in the colon of OXZ mice. Furthermore, nicotine suppressed CCL21-induced bone marrow-derived pDC migration due to Rac 1 inactivation, which was reversed by methyllycaconitine, a JAK2 inhibitor AG490 or caspase-3 inhibitor AZ-10417808. CCL21 was mainly expressed in the isolated lymphoid follicles (ILFs) of the colon during OXZ colitis. The therapeutic effect of cholinergic pathway on OXZ colitis probably through \u03b17nAChRs on pDCs were attributed to the suppression of pDC migration toward the ILFs. Therefore, the activation of \u03b17nAChRs has innovative therapeutic potential for the treatment of UC.<\/jats:p>","DOI":"10.1038\/s41598-021-04154-2","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T11:03:34Z","timestamp":1641553414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cholinergic anti-inflammatory pathway ameliorates murine experimental Th2-type colitis by suppressing the migration of plasmacytoid dendritic cells"],"prefix":"10.1038","volume":"12","author":[{"given":"Yuya","family":"Kanauchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaemin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusaku","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kadowaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"4154_CR1","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1053\/j.gastro.2011.02.016","volume":"140","author":"W Strober","year":"2011","unstructured":"Strober, W. & Fuss, I. J. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140, 1756\u20131767 (2011).","journal-title":"Gastroenterology"},{"key":"4154_CR2","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1136\/bmj.284.6317.706","volume":"284","author":"AD Harries","year":"1982","unstructured":"Harries, A. D., Baird, A. & Rhodes, J. Non-smoking: A feature of ulcerative colitis. Br. Med. J. (Clin. Res. Ed.) 284, 706 (1982).","journal-title":"Br. Med. J. (Clin. Res. Ed.)"},{"key":"4154_CR3","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1056\/NEJM198703193161202","volume":"316","author":"EJ Boyko","year":"1987","unstructured":"Boyko, E. J., Koepsell, T. D., Perera, D. R. & Inui, T. S. Risk of ulcerative colitis among former and current cigarette smokers. N. Engl. J. Med. 316, 707\u2013710 (1987).","journal-title":"N. Engl. J. Med."},{"key":"4154_CR4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1159\/000199478","volume":"37","author":"RJ Motley","year":"1987","unstructured":"Motley, R. J. et al. Time relationships between cessation of smoking and onset of ulcerative colitis. Digestion 37, 125\u2013127 (1987).","journal-title":"Digestion"},{"key":"4154_CR5","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1056\/NEJM199403243301202","volume":"330","author":"RD Pullan","year":"1994","unstructured":"Pullan, R. D. et al. Transdermal nicotine for active ulcerative colitis. N. Engl. J. Med. 330, 811\u2013815 (1994).","journal-title":"N. Engl. J. Med."},{"key":"4154_CR6","doi-asserted-by":"publisher","first-page":"364","DOI":"10.7326\/0003-4819-126-5-199703010-00004","volume":"126","author":"WJ Sandborn","year":"1997","unstructured":"Sandborn, W. J. et al. Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 126, 364\u2013371 (1997).","journal-title":"Ann. Intern. Med."},{"key":"4154_CR7","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1136\/bmj.289.6450.954","volume":"289","author":"KW Somerville","year":"1984","unstructured":"Somerville, K. W., Logan, R. F., Edmond, M. & Langman, M. J. Smoking and Crohn\u2019s disease. Br. Med. J. (Clin. Res. Ed.) 289, 954\u2013956 (1984).","journal-title":"Br. Med. J. (Clin. Res. Ed.)"},{"key":"4154_CR8","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/0016-5085(90)90324-T","volume":"98","author":"LR Sutherland","year":"1990","unstructured":"Sutherland, L. R., Ramcharan, S., Bryant, H. & Fick, G. Effect of cigarette smoking on recurrence of Crohn\u2019s disease. Gastroenterology 98, 1123\u20131128 (1990).","journal-title":"Gastroenterology"},{"key":"4154_CR9","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/ni1229","volume":"6","author":"WJ de Jonge","year":"2005","unstructured":"de Jonge, W. J. et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat. Immunol. 6, 844\u2013851 (2005).","journal-title":"Nat. Immunol."},{"key":"4154_CR10","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1053\/j.gastro.2007.07.022","volume":"133","author":"FO The","year":"2007","unstructured":"The, F. O. et al. Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in mice. Gastroenterology 133, 1219\u20131228 (2007).","journal-title":"Gastroenterology"},{"key":"4154_CR11","doi-asserted-by":"publisher","first-page":"e85888","DOI":"10.1371\/journal.pone.0085888","volume":"9","author":"T Yamamoto","year":"2014","unstructured":"Yamamoto, T. et al. Anti-allergic role of cholinergic neuronal pathway via \u03b17 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model. PLoS ONE 9, e85888 (2014).","journal-title":"PLoS ONE"},{"key":"4154_CR12","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/sj.bjp.0707264","volume":"151","author":"WJ de Jonge","year":"2007","unstructured":"de Jonge, W. J. & Ulloa, L. The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br. J. Pharmacol. 151, 915\u2013929 (2007).","journal-title":"Br. J. Pharmacol."},{"key":"4154_CR13","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.immuni.2017.06.008","volume":"46","author":"SS Chavan","year":"2017","unstructured":"Chavan, S. S., Pavlov, V. A. & Tracey, K. J. Mechanisms and therapeutic relevance of neuro-immune communication. Immunity 46, 927\u2013942 (2017).","journal-title":"Immunity"},{"key":"4154_CR14","doi-asserted-by":"publisher","first-page":"e0197487","DOI":"10.1371\/journal.pone.0197487","volume":"13","author":"E Meroni","year":"2018","unstructured":"Meroni, E. et al. Functional characterization of oxazolone-induced colitis and survival improvement by vagus nerve stimulation. PLoS ONE 13, e0197487 (2018).","journal-title":"PLoS ONE"},{"key":"4154_CR15","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nature01339","volume":"421","author":"H Wang","year":"2003","unstructured":"Wang, H. et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421, 384\u2013388 (2003).","journal-title":"Nature"},{"key":"4154_CR16","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1097\/00000658-196704000-00016","volume":"165","author":"M Tsukamoto","year":"1967","unstructured":"Tsukamoto, M. et al. Effect of vagal stimulation by 2-deoxy-d-glucose and insulin on gastric motility in dogs. Ann. Surg. 165, 605\u2013608 (1967).","journal-title":"Ann. Surg."},{"key":"4154_CR17","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1038\/sj.bjp.0705876","volume":"142","author":"L Piqueras","year":"2004","unstructured":"Piqueras, L. & Martinez, V. Peripheral GABAB agonists stimulate gastric acid secretion in mice. Br. J. Pharmacol. 142, 1038\u20131048 (2004).","journal-title":"Br. J. Pharmacol."},{"key":"4154_CR18","doi-asserted-by":"publisher","first-page":"134592","DOI":"10.1016\/j.neulet.2019.134592","volume":"714","author":"T Okumura","year":"2020","unstructured":"Okumura, T. et al. Brain orexin improves intestinal barrier function via the vagal cholinergic pathway. Neurosci. Lett. 714, 134592 (2020).","journal-title":"Neurosci. Lett."},{"key":"4154_CR19","doi-asserted-by":"publisher","first-page":"G968","DOI":"10.1152\/ajpgi.00346.2013","volume":"307","author":"S Hayashi","year":"2014","unstructured":"Hayashi, S. et al. Nicotine suppresses acute colitis and colonic tumorigenesis associated with chronic colitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 307, G968-978 (2014).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"4154_CR20","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1093\/ntr\/ntw245","volume":"19","author":"SD AlSharari","year":"2017","unstructured":"AlSharari, S. D. et al. Sex differences and drug dose influence the role of the \u03b17 nicotinic acetylcholine receptor in the mouse dextran sodium sulfate-induced colitis model. Nicotine Tob. Res. 19, 460\u2013468 (2017).","journal-title":"Nicotine Tob. Res."},{"key":"4154_CR21","doi-asserted-by":"publisher","first-page":"464","DOI":"10.2119\/molmed.2016.00062","volume":"22","author":"M Di Giovangiulio","year":"2016","unstructured":"Di Giovangiulio, M. et al. Vagotomy affects the development of oral tolerance and increases susceptibility to develop colitis independently of the alpha-7 nicotinic receptor. Mol. Med. 22, 464\u2013476 (2016).","journal-title":"Mol. Med."},{"key":"4154_CR22","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1053\/j.gastro.2006.08.016","volume":"131","author":"JE Ghia","year":"2006","unstructured":"Ghia, J. E., Blennerhassett, P., Kumar-Ondiveeran, H., Verdu, E. F. & Collins, S. M. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology 131, 1122\u20131130 (2006).","journal-title":"Gastroenterology"},{"key":"4154_CR23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s10020-020-00247-2","volume":"26","author":"BG Jo","year":"2020","unstructured":"Jo, B. G., Kim, S. H. & Namgung, U. Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats. Mol. Med. 26, 119 (2020).","journal-title":"Mol. Med."},{"key":"4154_CR24","doi-asserted-by":"publisher","first-page":"8686","DOI":"10.1073\/pnas.0500419102","volume":"102","author":"PJ Murray","year":"2005","unstructured":"Murray, P. J. The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription. Proc. Natl. Acad. Sci. USA 102, 8686\u20138691 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"4154_CR25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nri.2016.116","volume":"17","author":"T Worbs","year":"2017","unstructured":"Worbs, T., Hammerschmidt, S. I. & F\u00f6rster, R. Dendritic cell migration in health and disease. Nat. Rev. Immunol. 17, 30\u201348 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"4154_CR26","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.semcdb.2017.12.009","volume":"84","author":"C Macri","year":"2018","unstructured":"Macri, C., Pang, E. S., Patton, T. & O\u2019Keeffe, M. Dendritic cell subsets. Semin. Cell Dev. Biol. 84, 11\u201321 (2018).","journal-title":"Semin. Cell Dev. Biol."},{"key":"4154_CR27","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/j.1365-2249.2011.04439.x","volume":"166","author":"DC Baumgart","year":"2011","unstructured":"Baumgart, D. C. et al. Aberrant plasmacytoid dendritic cell distribution and function in patients with Crohn\u2019s disease and ulcerative colitis. Clin. Exp. Immunol. 166, 46\u201354 (2011).","journal-title":"Clin. Exp. Immunol."},{"key":"4154_CR28","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.immuni.2011.10.014","volume":"35","author":"H Takagi","year":"2011","unstructured":"Takagi, H. et al. Plasmacytoid dendritic cells are crucial for the initiation of inflammation and T cell immunity in vivo. Immunity 35, 958\u2013971 (2011).","journal-title":"Immunity"},{"key":"4154_CR29","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/mi.2016.96","volume":"10","author":"K Arimura","year":"2017","unstructured":"Arimura, K. et al. Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation. Mucosal Immunol. 10, 957\u2013970 (2017).","journal-title":"Mucosal Immunol."},{"key":"4154_CR30","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S1074-7613(02)00453-3","volume":"17","author":"F Heller","year":"2002","unstructured":"Heller, F., Fuss, I. J., Nieuwenhuis, E. E., Blumberg, R. S. & Strober, W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17, 629\u2013638 (2002).","journal-title":"Immunity"},{"key":"4154_CR31","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.autneu.2011.07.008","volume":"166","author":"J Lee","year":"2012","unstructured":"Lee, J., Yamamoto, T., Kuramoto, H. & Kadowaki, M. TRPV1 expressing extrinsic primary sensory neurons play a protective role in mouse oxazolone-induced colitis. Auton. Neurosci. 166, 72\u201376 (2012).","journal-title":"Auton. Neurosci."},{"key":"4154_CR32","doi-asserted-by":"publisher","first-page":"205873841877872","DOI":"10.1177\/2058738418778724","volume":"32","author":"JS Park","year":"2018","unstructured":"Park, J. S. et al. Combinatory treatment using tacrolimus and a STAT3 inhibitor regulate Treg cells and plasma cells. Int. J. Immunopathol. Pharmacol. 32, 2058738418778724 (2018).","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"4154_CR33","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1152\/physrev.1987.67.3.902","volume":"67","author":"J Gonella","year":"1987","unstructured":"Gonella, J., Bouvier, M. & Blanquet, F. Extrinsic nervous control of motility of small and large intestines and related sphincters. Physiol. Rev. 67, 902\u2013961 (1987).","journal-title":"Physiol. Rev."},{"key":"4154_CR34","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s00441-008-0684-7","volume":"334","author":"ZD Qu","year":"2008","unstructured":"Qu, Z. D. et al. Immunohistochemical analysis of neuron types in the mouse small intestine. Cell Tissue Res. 334, 147\u2013161 (2008).","journal-title":"Cell Tissue Res."},{"key":"4154_CR35","doi-asserted-by":"publisher","first-page":"e1720","DOI":"10.1371\/journal.pone.0001720","volume":"3","author":"JJ Smit","year":"2008","unstructured":"Smit, J. J. et al. The balance between plasmacytoid DC versus conventional DC determines pulmonary immunity to virus infections. PLoS ONE 3, e1720 (2008).","journal-title":"PLoS ONE"},{"key":"4154_CR36","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1126\/science.1099159","volume":"305","author":"F Benvenuti","year":"2004","unstructured":"Benvenuti, F. et al. Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming. Science 305, 1150\u20131153 (2004).","journal-title":"Science"},{"key":"4154_CR37","doi-asserted-by":"publisher","first-page":"11177","DOI":"10.1074\/jbc.M115.641514","volume":"290","author":"KA Silva","year":"2015","unstructured":"Silva, K. A. et al. Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia. J. Biol. Chem. 290, 11177\u201311187 (2015).","journal-title":"J. Biol. Chem."},{"key":"4154_CR38","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1038\/cdd.2017.111","volume":"24","author":"L Aram","year":"2017","unstructured":"Aram, L., Yacobi-Sharon, K. & Arama, E. CDPs: Caspase-dependent non-lethal cellular processes. Cell Death Differ. 24, 1307\u20131310 (2017).","journal-title":"Cell Death Differ."},{"key":"4154_CR39","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1084\/jem.188.10.1929","volume":"188","author":"M Boirivant","year":"1998","unstructured":"Boirivant, M., Fuss, I. J., Chu, A. & Strober, W. Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J. Exp. Med. 188, 1929\u20131939 (1998).","journal-title":"J. Exp. Med."},{"key":"4154_CR40","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1053\/j.gastro.2006.02.022","volume":"130","author":"DJ van Westerloo","year":"2006","unstructured":"van Westerloo, D. J. et al. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology 130, 1822\u20131830 (2006).","journal-title":"Gastroenterology"},{"key":"4154_CR41","doi-asserted-by":"publisher","first-page":"2314","DOI":"10.1016\/j.lfs.2007.02.036","volume":"80","author":"K Kawashima","year":"2007","unstructured":"Kawashima, K., Yoshikawa, K., Fujii, Y. X., Moriwaki, Y. & Misawa, H. Expression and function of genes encoding cholinergic components in murine immune cells. Life Sci. 80, 2314\u20132319 (2007).","journal-title":"Life Sci."},{"key":"4154_CR42","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00011-008-8171-x","volume":"58","author":"A Wongsriraksa","year":"2009","unstructured":"Wongsriraksa, A., Parsons, M. E. & Whelan, C. J. Characterisation of nicotine receptors on human peripheral blood mononuclear cells (PBMC). Inflamm. Res. 58, 38\u201344 (2009).","journal-title":"Inflamm. Res."},{"key":"4154_CR43","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1146\/annurev-immunol-042617-053158","volume":"36","author":"VA Pavlov","year":"2018","unstructured":"Pavlov, V. A., Chavan, S. S. & Tracey, K. J. Molecular and Functional Neuroscience in Immunity. Annu. Rev. Immunol. 36, 783\u2013812 (2018).","journal-title":"Annu. Rev. Immunol."},{"key":"4154_CR44","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.imlet.2004.06.003","volume":"95","author":"E Guinet","year":"2004","unstructured":"Guinet, E., Yoshida, K. & Nouri-Shirazi, M. Nicotinic environment affects the differentiation and functional maturation of monocytes derived dendritic cells (DCs). Immunol. Lett. 95, 45\u201355 (2004).","journal-title":"Immunol. Lett."},{"key":"4154_CR45","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.chom.2014.03.006","volume":"15","author":"S Dasgupta","year":"2014","unstructured":"Dasgupta, S., Erturk-Hasdemir, D., Ochoa-Reparaz, J., Reinecker, H. C. & Kasper, D. L. Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms. Cell Host Microbe 15, 413\u2013423 (2014).","journal-title":"Cell Host Microbe"},{"key":"4154_CR46","doi-asserted-by":"publisher","first-page":"803","DOI":"10.4049\/jimmunol.176.2.803","volume":"176","author":"MH Jang","year":"2006","unstructured":"Jang, M. H. et al. CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes. J. Immunol. 176, 803\u2013810 (2006).","journal-title":"J. Immunol."},{"key":"4154_CR47","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.4049\/jimmunol.1002598","volume":"186","author":"S Seth","year":"2011","unstructured":"Seth, S. et al. CCR7 essentially contributes to the homing of plasmacytoid dendritic cells to lymph nodes under steady-state as well as inflammatory conditions. J. Immunol. 186, 3364\u20133372 (2011).","journal-title":"J. Immunol."},{"key":"4154_CR48","doi-asserted-by":"crossref","unstructured":"Feagan, B. G., Rutgeerts, P., Sands, B. E., Hanauer, S., Colombel, J. F., Sandborn, W. J., Van Assche, G., Axler, J., Kim, H. J., Danese, S., Fox, I., Milch, C., Sankoh, S., Wyant, T., Xu, J. & Parikh, A. GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 369, 699\u2013710 (2013).","DOI":"10.1056\/NEJMoa1215734"},{"key":"4154_CR49","doi-asserted-by":"publisher","first-page":"111881","DOI":"10.1016\/j.biopha.2021.111881","volume":"141","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y., Yamamoto, T., Hayashi, S. & Kadowaki, M. Suppression of plasmacytoid dendritic cell migration to colonic isolated lymphoid follicles abrogates the development of colitis. Biomed. Pharmacother. 141, 111881 (2021).","journal-title":"Biomed. Pharmacother."},{"key":"4154_CR50","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1136\/jcp.2004.024828","volume":"58","author":"D Kawashima","year":"2005","unstructured":"Kawashima, D. et al. Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn\u2019s disease. J. Clin. Pathol. 58, 1057\u20131063 (2005).","journal-title":"J. Clin. Pathol."},{"key":"4154_CR51","doi-asserted-by":"publisher","first-page":"6338","DOI":"10.3748\/wjg.v11.i40.6338","volume":"11","author":"SM Cruickshank","year":"2005","unstructured":"Cruickshank, S. M., English, N. R., Felsburg, P. J. & Carding, S. R. Characterization of colonic dendritic cells in normal and colitic mice. World J. Gastroenterol. 11, 6338\u20136347 (2005).","journal-title":"World J. Gastroenterol."},{"key":"4154_CR52","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1084\/jem.188.2.373","volume":"188","author":"MC Dieu","year":"1998","unstructured":"Dieu, M. C. et al. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J. Exp. Med. 188, 373\u2013386 (1998).","journal-title":"J. Exp. Med."},{"key":"4154_CR53","doi-asserted-by":"publisher","first-page":"4923","DOI":"10.1182\/blood-2002-11-3474","volume":"101","author":"Y Yanagawa","year":"2003","unstructured":"Yanagawa, Y. & Ono\u00e9, K. CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities. Blood 101, 4923\u20134929 (2003).","journal-title":"Blood"},{"key":"4154_CR54","doi-asserted-by":"publisher","first-page":"2973","DOI":"10.1182\/blood-2007-09-112169","volume":"111","author":"K Gotoh","year":"2008","unstructured":"Gotoh, K. et al. Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells. Blood 111, 2973\u20132976 (2008).","journal-title":"Blood"},{"key":"4154_CR55","doi-asserted-by":"publisher","first-page":"20685","DOI":"10.1074\/jbc.273.33.20685","volume":"273","author":"DJ Mackay","year":"1998","unstructured":"Mackay, D. J. & Hall, A. Rho GTPases. J. Biol. Chem. 273, 20685\u201320688 (1998).","journal-title":"J. Biol. Chem."},{"key":"4154_CR56","doi-asserted-by":"publisher","first-page":"5716","DOI":"10.1128\/MCB.23.16.5716-5725.2003","volume":"23","author":"B Zhang","year":"2003","unstructured":"Zhang, B., Zhang, Y. & Shacter, E. Caspase 3-mediated inactivation of rac GTPases promotes drug-induced apoptosis in human lymphoma cells. Mol. Cell Biol. 23, 5716\u20135725 (2003).","journal-title":"Mol. Cell Biol."},{"key":"4154_CR57","doi-asserted-by":"publisher","first-page":"19656","DOI":"10.1074\/jbc.M009838200","volume":"276","author":"S Tu","year":"2001","unstructured":"Tu, S. & Cerione, R. A. Cdc42 is a substrate for caspases and influences Fas-induced apoptosis. J. Biol. Chem. 276, 19656\u201319663 (2001).","journal-title":"J. Biol. Chem."},{"key":"4154_CR58","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.cell.2004.06.020","volume":"118","author":"ER Geisbrecht","year":"2004","unstructured":"Geisbrecht, E. R. & Montell, D. J. A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Cell 118, 111\u2013125 (2004).","journal-title":"Cell"},{"key":"4154_CR59","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1159\/000235999","volume":"151","author":"T Watanabe","year":"2010","unstructured":"Watanabe, T. et al. The traditional herbal medicine saireito exerts its inhibitory effect on murine oxazolone-induced colitis via the induction of Th1-polarized immune responses in the mucosal immune system of the colon. Int. Arch. Allergy Immunol. 151, 98\u2013106 (2010).","journal-title":"Int. Arch. Allergy Immunol."},{"key":"4154_CR60","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1159\/000445433","volume":"169","author":"T Yamamoto","year":"2016","unstructured":"Yamamoto, T. et al. Induction of regulatory T cells as a novel mechanism underlying the therapeutic action of kakkonto, a traditional Japanese herbal medicine, in a murine food allergy model. Int. Arch. Allergy Immunol. 169, 146\u2013156 (2016).","journal-title":"Int. Arch. Allergy Immunol."},{"key":"4154_CR61","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1084\/jem.176.6.1693","volume":"176","author":"K Inaba","year":"1992","unstructured":"Inaba, K. et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte\/macrophage colony-stimulating factor. J. Exp. Med. 176, 1693\u20131702 (1992).","journal-title":"J. Exp. Med."},{"key":"4154_CR62","doi-asserted-by":"publisher","first-page":"6711","DOI":"10.4049\/jimmunol.169.12.6711","volume":"169","author":"P Brawand","year":"2002","unstructured":"Brawand, P. et al. Murine plasmacytoid pre-dendritic cells generated from Flt3 ligand-supplemented bone marrow cultures are immature APCs. J. Immunol. 169, 6711\u20136719 (2002).","journal-title":"J. Immunol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04154-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04154-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04154-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T20:17:57Z","timestamp":1669321077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04154-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["4154"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-04154-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,7]]},"assertion":[{"value":"28 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"54"}}