1. Jimmy Z Liu, Suzanne van Sommeren, Hailiang Huang, Siew C Ng, Rudi Alberts, Atsushi
Takahashi, Stephan Ripke, James C Lee, Luke Jostins, Tejas Shah, Shifteh Abedian, Jae Hee
Cheon, Judy Cho, Naser E Daryani, Lude Franke, Yuta Fuyuno, Ailsa Hart, Ramesh C Juyal,
Garima Juyal, Won Ho Kim, Andrew P Morris, Hossein Poustchi, William G Newman, Vandana
Midha, Timothy R Orchard, Homayon Vahedi, Ajit Sood, Joseph J Y Sung, Reza Malekzadeh,
Harm-Jan Westra, Keiko Yamazaki, Suk-Kyun Yang, International Multiple Sclerosis Genetics
Consortium, International IBD Genetics Consortium, Jeffrey C Barrett, Andre Franke, Behrooz Z
Alizadeh, Miles Parkes, Thelma B K, Mark J Daly, Michiaki Kubo, Carl A Anderson, Rinse K
Weersma. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and
highlight shared genetic risk across populations. Nat Genet; 47: 979–989, 2015
2. Katrina M de Lange, Loukas Moutsianas, James C Lee, Christopher A Lamb, Yang Luo,
Nicholas A Kennedy, Luke Jostins, Daniel L Rice, Javier Gutierrez-Achury, Sun-Gou Ji, Graham
Heap, Elaine R Nimmo, Cathryn Edwards, Paul Henderson, Craig Mowat, Jeremy Sanderson,
Jack Satsangi, Alison Simmons, David C Wilson, Mark Tremelling, Ailsa Hart, Christopher G
Mathew, William G Newman, Miles Parkes, Charlie W Lees, Holm Uhlig, Chris Hawkey, Natalie
J Prescott, Tariq Ahmad, John C Mansfield, Carl A Anderson, Jeffrey C Barrett. Genome-wide
association study implicates immune activation of multiple integrin genes in inflammatory bowel
disease. Nat Genet; 49: 256–261, 2017
3. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP,
Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL,
Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L,
Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A,
61
Boucher G, Brand S, Büning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL,
Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R,
Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH,
Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G,
Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott
NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms
LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga
C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H. International
IBD Genetics Consortium (IIBDGC), Silverberg MS, Annese V, Hakonarson H, Brant SR,
Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S,
Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of
inflammatory bowel disease. Nature; 491:119-124, 2012
4. Franke A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr G, Domingues FS,
Albrecht M, Nothnagel M, Ellinghaus D, Sina C, Onnie CM, Weersma RK, Stokkers PC,
Wijmenga C, Gazouli M, Strachan D, McArdle WL, Vermeire S, Rutgeerts P, Rosenstiel P,
Krawczak M, Vatn MH; IBSEN study group, Mathew CG, Schreiber S. Sequence variants in
IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nature
Genetics; 40: 1319-1323, 2008
5. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A,
Henderson WR Jr, Muller W, Rudensky AY. Regulatory T cell-derived interleukin-10 limits
inflammation at environmental interfaces. Immunity; 28: 546–558, 2008
6. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop
chronic enterocolitis. Cell; 75: 263–274, 1993
62
7. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C,
Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa
S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki
H, Kikuchi J, Honda K, Hase K, Ohno H. Commensal microbe-derived butyrate induces the
differentiation of colonic regulatory T cells. Nature; 504: 446-450, 2013
8. Nicholas Arpaia, Clarissa Campbell, Xiying Fan, Stanislav Dikiy, Joris van der Veeken, Paul
deRoos, Hui Liu, Justin R. Cross, Klaus Pfeffer, Paul J. Coffer, Alexander Y. Rudensky.
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Nature; 504: 451–455, 2013
9. Heimesaat MM, Bereswill S, Fischer A, Fuchs D, Struck D, Niebergall J, Jahn HK, Dunay IR,
Moter A, Gescher DM, Schumann RR, Göbel UB, Liesenfeld O. Gram-negative bacteria
aggravate murine small intestinal Th1-type immunopathology following peroral infection with
Toxoplasma gondii. J Immunol; 177: 8785-95, 2006
10. Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA,
Swidsinski A, Beaugerie L, Colombel JF. High prevalence of adherent-invasive Escherichia coli
associated with ileal mucosa in Crohn’s disease. Gastroenterol; 127: 412-421, 2004
11. Johnson GJ, Cosnes J, Mansfield JC. Smoking cessation as primary therapy tomodify the
course of Crohn’s disease. Aliment Pharmacol Ther; 21: 921-931, 2005
12. Aldhous MC, Drummond HE, Anderson N, Baneshi MR, Smith LA, Arnott ID, Satsangi J.
Smoking habit and load influence age at diagnosis and disease extent in ulcerative colitis. Am J
Gastroenterol; 102: 589-597, 2007
13. Boyko EJ, Perera DR, Koepsell TD, Keane EM, Inui TS. Effects of cigarette smoking on the
clinical course of ulcerative colitis. Scand J Gastroenterol; 23: 1147-1152, 1988
14. Mokbel M, Carbonnel F, Beaugerie L, Gendre JP, Cosnes J. Effect of smoking on the
63
long-term course of ulcerative colitis. Gastroenterol Clin Biol; 22: 858-862, 1998
15 Cosnes J. Tobacco and IBD: relevance in the understanding of disease mechanisms and
clinical practice. Best Pract Res Clin Gastroenterol; 18: 481–96, 2004
16. Srivastava ED, Russell MAH, Feyerabend C, Williams GT, Masterton JG, Rhodes J.
Transdermal nicotine in active ulcerative colitis. Eur J Gastroenterol Hepatol; 3:875–878, 1991
17. Guslandi M, Tittobello A. Steroid-sparing effect of transdermal nicotine in ulcerative colitis. J
Clin Gastroenterol; 18: 347–348, 1994
18. Rupert D. Pullan, John Rhodes, Subramanian Ganesh, Venk Mani, John S. Morris, Geraint T.
Williams, Robert G. Newcombe, Michael Russell, Colin Feyerabend, Gareth Thomas, Urbain
Sawe. Transdermal nicotine for active ulcerative colitis. N Engl J Med; 330: 811–815, 1994
19. Sandborn WJ, Tremaine WJ, Offord KP, Lawson GM, Petersen BT, Batts KP, Croghan IT,
Dale LC, Schroeder DR, Hurt RD. Transdermal nicotine for mildly to moderately active
ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med;
126:364–371, 1997
20. Hana Florian, Andreas Meier, Serge Gauthier, Stanley Lipschitz, Yunzhi Lin, Qi Tang, Ahmed
A Othman, Weining Z Robieson, Laura M Gault. Efficacy and Safety of ABT-126 in Subjects
with Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors:
A Randomized, Double-Blind, Placebo-Controlled Study. J Alzheimers Dis; 51(4): 1237-47,
2016
21. Robert Freedman 1, Ann Olincy, Robert W Buchanan, Josette G Harris, James M Gold, Lynn
Johnson, Diana Allensworth, Alejandrina Guzman-Bonilla, Bettye Clement, M Patricia Ball, Jay
Kutnick, Vicki Pender, Laura F Martin, Karen E Stevens, Brandie D Wagner, Gary O Zerbe,
Ferenc Soti, William R Kem. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J
Psychiatry; 165(8): 1040-7, 2008
64
22. J R Ingram, P Routledge, J Rhodes, R W Marshall, D C Buss, B K Evans, C Feyerabend, G A
O Thomas. Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics
and adverse events associated with three doses of nicotine. Aliment Pharmacol Ther; 20(8):
859-65, 2004
23. Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, Kamochi H, Suzuki N.
Nicotine inhibits the production of proinflammatory mediators in human monocytes by
suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity
through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol; 146: 116–123, 2006
24. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ,
Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE. Stimulation of the
vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway.
Nat Immunol; 6: 844–851, 2005
25. Kawashima K, Yoshikawa K, Fujii YX, Moriwaki Y, Misawa H.Expression and function of
genes encoding cholinergic components in murine immune cells. Life Sci; 80: 2314–2319, 2007
26. Koval LM, Yu Lykhmus O, Omelchenko DM, Komisarenko SV, Skok MV. The role of alpha7
nicotinic acetylcholine receptors in B lymphocyte activation. Ukr Biokhim Zh; 81: 5–11, 2009
27. Razani-Boroujerdi S, Boyd RT, Dávila-García MI, Nandi JS, Mishra NC, Singh SP,
Pena-Philippides JC, Langley R, Sopori ML. T cells express alpha7-nicotinic acetylcholine
receptor subunits that require a functional TCR and leukocyte-specific protein tyrosine kinase for
nicotine-induced Ca2+ response. J Immunol; 179: 2889–2898, 2007
28. Su X, Matthay MA, Malik AB. Requisite role of the cholinergic alpha7 nicotinic
acetylcholine receptor pathway in suppressing Gram-negative sepsis-induced acute lung
inflammatory injury. J Immunol;184: 401–410, 2010
29. Yamamoto T, Kodama T, Lee J, Utsunomiya N, Hayashi S, Sakamoto H, Kuramoto H,
65
Kadowaki M. Anti-allergic role of cholinergic neuronal pathway via alpha7 nicotinic ACh
receptors on mucosal mast cells in a murine food allergy model. PLoS One; 9: e85888, 2014
30. Felten DL, Felten SY, Carlson SL, Olschowka JA, Livnat S. Noradrenergic and peptidergic
innervation of lymphoid tissue. J Immunol; 135:755s-765s,1985
31. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad
N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response
to endotoxin. Nature; 405: 458–462, 2000
32. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa
L, Al-Abed Y, Czura CJ, Tracey KJ. Nicotinic acetylcholine receptor alpha7 subunit is an
essential regulator of inflammation. Nature; 421: 384-388, 2003
33. Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C,
Miller EJ, Tracey KJ, Ulloa L. Cholinergic agonists inhibit HMGB1 release and improve survival
in experimental sepsis. Nat Med; 10: 1216–1221, 2004
34. Tracey, K.J. Reflex control of immunity. Nat Rev Immunol; 9: 418−428, 2009.
35. Sun P, Zhou K, Wang S, Li P, Chen S, Lin G, Zhao Y, Wang T. Involvement of
MAPK/NF-kappaB signaling in the activation of the cholinergic anti-inflammatory pathway in
experimental colitis by chronic vagus nerve stimulation. PLoS One; 8: e69424, 2013
36. Bertrand D, Lee CH, Flood D, Marger F, Donnelly-Roberts D. Therapeutic potential of
alpha7 nicotinic acetylcholine receptors. Pharmacol Rev; 67: 1025–1073, 2015
37. Gotti C, Clementi F. Neuronal nicotinic receptors: from structure to pathology. Prog
Neurobiol; 74: 363–396, 2004
38. Su X, Matthay MA, Malik AB. Requisite role of the cholinergic alpha7 nicotinic
acetylcholine receptor pathway in suppressing Gram-negative sepsis-induced acute lung
inflammatory injury. J Immunol; 184:401–410, 2010
66
39. Nugent FW, Roy MA. Duodenal Crohn’s disease: an analysis of 89 cases. Am J
Gastroenterol; 84: 249–254, 1989
40. Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM. The vagus nerve: a
tonic inhibitory influence associated with inflammatory bowel disease in a murine model.
Gastroenterology;131: 1122–1130, 2006
41. Chatterjee PK, Al-Abed Y, Sherry B, Metz CN. Cholinergic agonists regulate JAK2/STAT3
signaling to suppress endothelial cell activation. Am J Physiol Physiol; 297: C1294–C306, 2009
42. AlSharari SD, Bagdas D, Akbarali HI, Lichtman PA, Raborn ES, Cabral GA, Carroll FI,
McGee EA, Damaj MI. Sex Differences and Drug Dose Influence the Role of the α7 Nicotinic
Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model. Nicotine
Tob Res; 19: 460–468, 2017
43. Eliakim R, Fan QX, Babyatsky MW. Chronic nicotine administration differentially alters
jejunal and colonic inflammation in interleukin-10 deficient mice. Eur J Gastroenterol Hepatol;
14: 607-14, 2002
44. Cailotto C, Costes LM, van der Vliet J, van Bree SH, van Heerikhuize JJ, Buijs RM,
Boeckxstaens GE. Neuroanatomical evidence demonstrating the existence of the vagal
anti‐inflammatory reflex in the intestine. Neurogastroenterol Motil; 24: 191-200, e93, 2012
45. Nemethova A, Michel K, Gomez-Pinilla PJ, Boeckxstaens GE, Schemann M. Nicotine
attenuates activation of tissue resident macrophages in the mouse stomach through the beta2
nicotinic acetylcholine receptor. PLoS One; 8: e79264, 2013
46. Matteoli G, Gomez‐Pinilla PJ, Nemethova A, Di GM, Cailotto C, van Bree SH, Michel K,
Tracey KJ, Schemann M, Boesmans W, Vanden Berghe P, Boeckxstaens GE. A distinct vagal
anti‐inflammatory pathway modulates intestinal muscularis resident macrophages independent of
the spleen. Gut; 63: 938-948, 2014
67
47. Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta
M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L. Splenectomy inactivates the cholinergic
antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med; 203:
1623-1628, 2006
48. Yang WL, Frucht H. Cholinergic receptor up-regulates COX-2 expression and prostaglandin
E2 production in colon cancer cells. Carcinogenesis; 21:1789–1793, 2000
49. Gustafsson JK, Ermund A, Johansson ME, Schütte A, Hansson GC, Sjövall H. An ex vivo
method for studying mucus formation, properties, and thickness in human colonic biopsies and
mouse small and large intestinal explants. Am J Physiol Gastrointest Liver Physiol; 302:
G430-438, 2012
50. Birchenough GM, Nyström EE, Johansson ME, Hansson GC. A sentinel goblet cell guards
the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science; 352: 1535-1542, 2016
51. McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V, Knoop KA, Newberry RD,
Miller MJ. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine.
Nature; 483: 345-349, 2012
52. Fujii T, Mashimo M, Moriwaki Y, Misawa H, Ono S, Horiguchi K, Kawashima K. Expression
and Function of the Cholinergic System in Immune Cells. Front Immunol; 8: 1085, 2017
53. Fujii T, Mashimo M, Moriwaki Y, Misawa H, Ono S, Horiguchi K, Kawashima K.
Physiological functions of the cholinergic system in immune cells. J Pharmacol Sci; 134: 1-21,
2017
54. Ihara S, Hirata Y, Serizawa T, Suzuki N, Sakitani K, Kinoshita H, Hayakawa Y, Nakagawa H1,
Ijichi H, Tateishi K, Koike K. TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis
by Controlling Epithelial Differentiation and the Luminal Microbiota. J Immunol; 196:
4603-4613, 2016
68
55. Ihara S, Hirata Y, Hikiba Y, Yamashita A, Tsuboi M, Hata M, Konishi M, Suzuki N, Sakitani
K, Kinoshita H, Hayakawa Y, Nakagawa H, Ijichi H, Tateishi K, Koike K. Adhesive Interactions
between Mononuclear Phagocytes and Intestinal Epithelium Perturb Normal Epithelial
Differentiation and Serve as a Therapeutic Target in Inflammatory Bowel Disease. J Crohns
Colitis;12: 1219-1231, 2018
56. N L Benowitz, P Jacob 3rd. Daily intake of nicotine during cigarette smoking. Clin Pharmacol
Ther; 35(4): 499-504, 1984
57. Janne Hukkanen 1, Peyton Jacob 3rd, Neal L Benowitz. Metabolism and disposition kinetics
of nicotine. Pharmacol Rev; 57(1): 79-115, 2005
58. Inaba K, Swiggard WJ, Steinman RM, Romani N, Schuler G, Brinster C. Isolation of
Dendritic Cells. Curr Protoc Immunol; 86:3.7.1-3.7.19, 2009
59. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A,
Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro
without a mesenchymal niche. Nature; 459: 262–265, 2009
60. Caterina M Hernandez, Ibdanelo Cortez, Zhenglin Gu, José O Colón-Sáez, Patricia W Lamb,
Maki Wakamiya, Jerrel L Yakel, and Kelly T Dineley. Research tool: validation of floxed α7
nicotinic acetylcholine receptor conditional knockout mice using in vitro and in vivo approaches.
J Physiol; 592(Pt 15): 3201–3214, 2014
61. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM,
Sartor RB. Resident enteric bacteria are necessary for development of spontaneous colitis and
immune system activation in interleukin-10-deficient mice. Infect Immun; 66: 5224–5231, 1998
62. Jane L Benjamin, Charlotte R H Hedin, Andreas Koutsoumpas, Siew C Ng, Neil E McCarthy,
Natalie J Prescott, Pedro Pessoa-Lopes, Christopher G Mathew, Jeremy Sanderson, Ailsa L Hart,
Michael A Kamm, Stella C Knight, Alastair Forbes, Andrew J Stagg, James O Lindsay, Kevin
69
Whelan. Smokers with active Crohn's disease have a clinically relevant dysbiosis of the
gastrointestinal microbiota. Inflamm Bowel Dis; 18: 1092–1100, 2012
63. Hui Wang, Jun-Xing Zhao, Nan Hu, Jun Ren, Min Du, Mei-Jun Zhu. Side-stream smoking
reduces intestinal inflammation and increases expression of tight junction proteins. World J
Gastroenterol; 18: 2180–2187, 2012
64. Amy R. Sapkota, Sibel Berger, Timothy M. Vogel. Human Pathogens Abundant in the
Bacterial Metagenome of Cigarettes. Environ Health Perspect; 118: 351–356, 2010
65. Luc Biedermann, Karin Brülisauer, Jonas Zeitz, Pascal Frei, Michael Scharl, Stephan R
Vavricka, Michael Fried, Martin J Loessner, Gerhard Rogler, Markus Schuppler. Smoking
cessation alters intestinal microbiota: insights from quantitative investigations on human fecal
samples using FISH. Inflamm Bowel Dis; 20: 1496–1501, 2014
66. Luc Biedermann, Jonas Zeitz,Jessica Mwinyi, Eveline Sutter-Minder, Ateequr Rehman,
Stephan J. Ott, Claudia Steurer-Stey, Anja Frei, Pascal Frei, Michael Scharl, Martin J. Loessner,
Smoking Cessation Induces Profound Changes in the Composition of the Intestinal Microbiota in
Humans. PLoS One; 8: e59260, 2013
67. Koichi Tomoda, Kaoru Kubo, Kazuo Hino, Yasunori Kondoh, Yasue Nishii, Noriko Koyama,
Yoshifumi Yamamoto, Masanori Yoshikawa, Hiroshi Kimura. Branched-chain amino acid-rich
diet improves skeletal muscle wasting caused by cigarette smoke in rats. J Toxicol Sci; 36:
261–266, 2014
68. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. The inner of the
two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S
A; 105: 15064-15069, 2008
69. Van der Sluis M, De Koning BA, De Bruijn AC, Velcich A, Meijerink JP, Van Goudoever JB,
Büller HA, Dekker J, Van Seuningen I, Renes IB, Einerhand AW. Muc2-deficient mice
70
spontaneously develop colitis, indicating that MUC2 is critical for colonic protection.
Gastroenterology; 131: 117-29, 2006
70. van der Post S, Jabbar KS, Birchenough G, Arike L, Akhtar N, Sjovall H, Johansson MEV,
Hansson GC. Structural weakening of the colonic mucus barrier is an early event in ulcerative
colitis pathogenesis. Gut; 68: 2142-2151, 2019
71. Johansson ME, Gustafsson JK, Holmén-Larsson J, Jabbar KS, Xia L, Xu H, Ghishan FK,
Carvalho FA, Gewirtz AT, Sjövall H, Hansson GC. Bacteria penetrate the normally impenetrable
inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut;
63: 281-291, 2014
72. Gersemann M, Becker S, Kübler I, Koslowski M, Wang G, Herrlinger KR, Griger J, Fritz P,
Fellermann K, Schwab M, Wehkamp J, Stange EF. Differences in goblet cell differentiation
between Crohn's disease and ulcerative colitis. Differentiation; 77: 84-94, 2009
73. Jenny K Gustafsson, Anna Ermund, Malin E V Johansson, André Schütte, Gunnar C Hansson,
Henrik Sjövall. An ex vivo method for studying mucus formation, properties, and thickness in
human colonic biopsies and mouse small and large intestinal explants. Am J Physiol Gastrointest
Liver Physiol; 302(4): G430-8, 2012
74. Sophie Laffont, Karima R R Siddiqui, Fiona Powrie. Intestinal inflammation abrogates the
tolerogenic properties of MLN CD103+ dendritic cells.
Eur J Immunol; 40(7): 1877-83, 2010
75. Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian
UH. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature; 424:
88-93, 2003
76. Johansson-Lindbom B, Svensson M, Pabst O, Palmqvist C, Marquez G, Förster R, Agace
WW. Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective
T cell homing. J Exp Med; 202: 1063-73, 2005
71
77. Jan Hendrik Niess, Guido Adler. Enteric flora expands gut lamina propria CX3CR1+
dendritic cells supporting inflammatory immune responses under normal and inflammatory
conditions. J Immunol; 184(4): 2026-37, 201078. Bain CC, Schridde A. Origin, Differentiation,
and Function of Intestinal Macrophages. Front Immunol; 9: 2733, 2018
79. De Schepper S, Verheijden S, Aguilera-Lizarraga J, Viola MF, Boesmans W, Stakenborg N,
Voytyuk I, Schmidt I, Boeckx B, Dierckx de Casterlé I, Baekelandt V, Gonzalez Dominguez E,
Mack M, Depoortere I, De Strooper B, Sprangers B, Himmelreich U, Soenen S, Guilliams M,
Vanden Berghe P, Jones E, Lambrechts D, Boeckxstaens G. Self-Maintaining Gut Macrophages
Are Essential for Intestinal Homeostasis. Cell; 175: 400-415, e13, 2018
80. Alkhattabi N, Todd I, Negm O, Tighe PJ, Fairclough LC. Tobacco smoke and nicotine
suppress expression of activating signaling molecules in human dendritic cells. Toxicology
Letters; 299: 40-46, 2018
81. Dror S Shouval, Jodie Ouahed, Amlan Biswas, Jeremy A Goettel , Bruce H Horwitz,
Christoph Klein , Aleixo M Muise, Scott B Snapper. Interleukin 10 receptor signaling: master
regulator of intestinal mucosal homeostasis in mice and humans. Adv Immunol; 122: 177-210,
2014
82. Shakir D AlSharari, Deniz Bagdas, Hamid I Akbarali, Patraic A Lichtman, Erinn S Raborn,
Guy A Cabral, F Ivy Carroll, Elizabeth A McGee, M Imad Damaj. Sex Differences and Drug
Dose Influence the Role of the α7 Nicotinic Acetylcholine Receptor in the Mouse Dextran
Sodium Sulfate-Induced Colitis Model. Nicotine Tob Res; 19(4): 460-468, 2017
72
謝辞
本論文の作成に当たり、懇切なるご指導ならびにご鞭撻を賜りました、東京大学大学
院医学系研究科 消化器内科学
小池和彦教授に謹んで御礼を申し上げます。
また、本研究の遂行にあたり多大なるご協力を賜りました、東京大学医科学研究所
端ゲノム医学分野 平田喜裕准教授に深く感謝申し上げます。
その他、様々な点でご協力、ご指導頂きました東京大学消化器内科の先生方に感謝申
し上げます。
73
...