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DOI: 10.1055/s-2002-32808
Role of the Intestinal Epithelium in Orchestrating Innate and Adaptive Mucosal Immunity
Rolle des intestinalen Epithels im Rahmen der angeborenen und erworbenen ImmunitätPublication History
Manuscript received: 10. December 2001
Accepted after revision: 17. December 2001
Publication Date:
15 July 2002 (online)

Zusammenfassung
Die Mukosa, welche das humane Kolon und den Dünndarm begrenzt, ist ein Gebiet von chronischer, regulierter, „physiologischer” Entzündung. Dies stellt einen deutlichen Gegensatz zu anderen mukosalen Gebieten des Körpers dar, denn fänden sich die gleiche Anzahl von T- und B-Lymphozyten, Eosinophilen, Mastzellen, Makrophagen und dendritischen Zellen, wie sie im humanen Intestinaltrakt vorhanden sind, in anderen Bereichen, so würde man diese Orte als Orte von chronisch pathologischer Entzündung bezeichnen. Diese Übersicht beschreibt die Rolle des intestinalen Epithels bei der Entstehung dieser „physiologischen”, intestinalen, mukosalen Entzündung und konzentriert sich dabei auf dessen Rolle im Rahmen der Initiierung und Vermittlung von angeborenen und erworbenen mukosalen Immunantworten.
Abstract
The mucosa that lines the human colon and small intestine is a site of chronic regulated “physiologic” inflammation. This contrasts markedly with other mucosal sites in that if the numbers of T and B cells, eosinophils, mast cells, macrophages, and dendritic cells that are present in the human intestinal tract were to be present in other sites, those sites would be considered to be sites of chronic pathological inflammation. This review examines the role of the intestinal epithelium in the development of “physiologic” intestinal mucosal inflammation and focuses on its role in signalling and mediating host innate and adaptive mucosal immune responses.
Schlüsselwörter
Epithelzelle - Chemokin - Zytokin - Wirtsabwehr - Pathogene Bakterien
Key words
Epithelial Cell - Chemokine - Cytokine - Host Defence - Pathogenic Bacteria
References
- 1
Anderson J M, Van
Itallie C M.
Tight junctions: closing in on the seal.
Curr
Biol.
1999;
9
R922-924
MissingFormLabel
- 2
Youakim A, Ahdieh M.
Interferon-gamma decreases barrier function in T84 cells by
reducing ZO-1 levels and disrupting apical actin.
Am J
Physiol.
1999;
276
G1279-1288
MissingFormLabel
- 3
Kucharzik T, Walsh S V, Chen J, Parkos C A, Nusrat A.
Neutrophil transmigration in inflammatory bowel disease is
associated with differential expression of epithelial intercellular junction
proteins.
Am J
Pathol.
2001;
159
2001-2009
MissingFormLabel
- 4
Dignass A U, Podolsky D K.
Cytokine modulation of intestinal epithelial cell
restitution: central role of transforming growth factor
beta.
Gastroenterology.
1993;
105
1323-1332
MissingFormLabel
- 5
Dignass A, Lynch-Devaney K, Kindon H, Thim L, Podolsky D K.
Trefoil peptides promote epithelial migration through a
transforming growth factor beta-independent pathway.
J Clin
Invest.
1994;
94
376-383
MissingFormLabel
- 6
Eckmann L, Kagnoff M F, Fierer J.
Epithelial cells secrete the chemokine interleukin-8 in
response to bacterial entry.
Infect
Immun.
1993;
61
4569-4574
MissingFormLabel
- 7
Jung H C, Eckmann L, Yang S K. et al .
A distinct array of proinflammatory cytokines is expressed in
human colon epithelial cells in response to bacterial invasion.
J
Clin
Invest.
1995;
95
55-65
MissingFormLabel
- 8
Yang S K, Eckmann L, Panja A, Kagnoff M F.
Differential and regulated expression of C-X-C, C-C, and
C-chemokines by human colon epithelial
cells.
Gastroenterology.
1997;
113
1214-1223
MissingFormLabel
- 9
Reinecker H C, Loh E Y, Ringler D J, Mehta A, Rombeau J L, MacDermott R P.
Monocyte-chemoattractant protein 1 gene expression in
intestinal epithelial cells and inflammatory bowel disease
mucosa.
Gastroenterology.
1995;
108
40-50
MissingFormLabel
- 10
Izadpanah A, Dwinell M B, Eckmann L, Varki N M, Kagnoff M F.
Regulated MIP-3alpha/CCL20 production by human intestinal
epithelium: mechanism for modulating mucosal immunity.
Am J Physiol
Gastrointest Liver
Physiol.
2001;
280
G710-719
MissingFormLabel
- 11
Dwinell M B, Lugering N, Eckmann L, Kagnoff M F.
Regulated Production of Interferon-Inducible T-Cell
Chemoattractants by Human Intestinal Epithelial
Cells.
Gastroenterology.
2001;
120
49-59
MissingFormLabel
- 12
Shibahara T, Wilcox J N, Couse T, Madara J L.
Characterization of Epithelial Chemoattractants for Human
Intestinal Intraepithelial
Lymphocytes.
Gastroenterology.
2001;
120
60-70
MissingFormLabel
- 13
Kunkel E J, Campbell J J, Haraldsen G. et al .
Lymphocyte CC chemokine receptor 9 and epithelial
thymus-expressed chemokine (TECK) expression distinguish the small intestinal
immune compartment: Epithelial expression of tissue-specific chemokines as an
organizing principle in regional immunity.
J Exp
Med.
2000;
192
761-768
MissingFormLabel
- 14
Wurbel M A, Philippe J M, Nguyen C. et al .
The chemokine TECK is expressed by thymic and intestinal
epithelial cells and attracts double- and single-positive thymocytes expressing
the TECK receptor CCR9.
Eur J
Immunol.
2000;
30
262-271
MissingFormLabel
- 15
Pan J, Kunkel E J, Gosslar U. et al .
A novel chemokine ligand for CCR10 and CCR3 expressed by
epithelial cells in mucosal tissues.
J
Immunol.
2000;
165
2943-2949
MissingFormLabel
- 16
Wang W, Soto H, Oldham E R. et al .
A. Identification of a novel chemokine (CCL28), which binds
CCR10 (GPR2).
J Biol Chem
2000.
275
22313-22323
MissingFormLabel
- 17
Reinecker H C, MacDermott R P, Mirau S, Dignass A, Podolsky D K.
Intestinal epithelial cells both express and respond to
interleukin
15.
Gastroenterology.
1996;
111
1706-1713
MissingFormLabel
- 18
Eckmann L, Reed S L, Smith J R, Kagnoff M F.
Entamoeba histolytica trophozoites induce an inflammatory
cytokine response by cultured human cells through the paracrine action of
cytolytically released interleukin-1 alpha.
J Clin
Invest.
1995;
96
1269-1279
MissingFormLabel
- 19
Maaser C, Eckmann L, Paesold G, Kim H S, Kagnoff M F.
Ubiquitous production of macrophage migration inhibitory
factor by human gastric and intestinal
epithelium.
Gastroenterology.
2002;
122
667-680
MissingFormLabel
- 20
Maaser C, Eckmann L, Birkenbach M P, Kagnoff M F.
Human intestinal epithelium expresses EBI3, a potential
modulator of the IL-12
response.
Gastroenterology.
2001;
120
A-994
MissingFormLabel
- 21
Maaser C, Schoeppner S, Kucharzik T, Kraft M, Schoenherr E, Domschke W, Luegering N.
Colonic epithelial cells induce endothelial cell expression
of ICAM-1 and VCAM-1 by a NF-kappaB-dependent mechanism.
Clin Exp
Immunol.
2001;
124
208-213
MissingFormLabel
- 22
Eckmann L, Jung H C, Schurer-Maly C, Panja A, Morzycka-Wroblewska E, Kagnoff M F.
Differential cytokine expression by human intestinal
epithelial cell lines: regulated expression of interleukin
8.
Gastroenterology.
1993;
105
1689-1697
MissingFormLabel
- 23
Hase K, Eckmann L, Leopard J D, Varki N, Kagnoff M F.
Cell Differentiation Is a Key Determinant of Cathelicidin
LL-37/Human Cationic Antimicrobial Protein 18 Expression by Human Colon
Epithelium.
Infect
Immun.
2002;
70
953-963
MissingFormLabel
- 24
O’Neil D A, Porter E M, Elewaut D, Anderson G M, Eckmann L, Ganz T, Kagnoff M F.
Expression and regulation of the human beta-defensins hBD-1
and hBD-2 in intestinal epithelium.
J
Immunol.
1999;
163
6718-6724
MissingFormLabel
- 25
O’Neil D A, Cole S P, Martin-Porter E, Housley M P, Liu L, Ganz T, Kagnoff M F.
Regulation of human beta-defensins by gastric epithelial
cells in response to infection with Helicobacter pylori or stimulation with
interleukin-1.
Infect
Immun.
2000;
68
5412-5415
MissingFormLabel
- 26
Witthoft T, Eckmann L, Kim J M, Kagnoff M F.
Enteroinvasive bacteria directly activate expression of iNOS
and NO production in human colon epithelial cells.
Am J
Physiol.
1998;
275
G564-571
MissingFormLabel
- 27
Eckmann L, Stenson W F, Savidge T C, Lowe D C, Barrett K E, Fierer J, Smith J R, Kagnoff M F.
Role of intestinal epithelial cells in the host secretory
response to infection by invasive bacteria. Bacterial entry induces epithelial
prostaglandin h synthase-2 expression and prostaglandin E2 and F2alpha
production.
J Clin Invest
1997.
100
296-309
MissingFormLabel
- 28 Casanova J E. Structure and function of the polimeric immunoglobulin
receptor in epithelial cells. Kagnoff MF, H Kiyono
H Essentials of mucosal immunology San
Diego; Academic 1996: 151-166
MissingFormLabel
- 29
Mestecky J, Lue C, Russell M W.
Selective transport of IgA. Cellular and molecular
aspects.
Gastroenterol Clin North.
Am
1991;
20
441-471
MissingFormLabel
- 30
Mazanec M B, Kaetzel C S, Lamm M E, Fletcher D, Nedrud J G.
Intracellular neutralization of virus by immunoglobulin A
antibodies.
Proc Natl Acad Sci U S
A.
1992;
89
6901-6905
MissingFormLabel
- 31
Burns J W, Siadat-Pajouh M, Krishnaney A A, Greenberg H B.
Protective effect of rotavirus VP6-specific IgA monoclonal
antibodies that lack neutralizing
activity.
Science.
1996;
272
104-107
MissingFormLabel
- 32 Colgan S P, Hershberg R M, Furuta G T, Blumberg R S. Ligation of intestinal epithelial CD1d induces bioactive
IL-10: critical role of the cytoplasmic tail in autocrine signaling. U
S A; Proc Natl Acad
Sci 1999 96: 13938-13943
MissingFormLabel
- 33 Steinle A, Groh V, Spies T. Diversification, expression, and gamma delta T cell
recognition of evolutionarily distant members of the MIC family of major
histocompatibility complex class I-related molecules. Proc Natl
Acad Sci U S
A; 1998 95: 12510-12515
MissingFormLabel
- 34 Varilek G W, Neil G A, Bishop W P. Caco-2 cells express type I interleukin-1 receptors: ligand
binding enhances proliferation. Am J
Physiol 1994 267: G1101-1107
MissingFormLabel
- 35
Colgan S P, Resnick M B, Parkos C A. et al .
IL-4 directly modulates function of a model human intestinal
epithelium.
J
Immunol.
1994;
153
2122-2129
MissingFormLabel
- 36
Reinecker H C, Podolsky D K.
Human intestinal epithelial cells express functional cytokine
receptors sharing the common gamma c chain of the interleukin 2
receptor.
Proc Natl Acad Sci U S
A.
1995;
92
8353-8357
MissingFormLabel
- 37
Yamada K, Shimaoka M, Nagayama K, Hiroi T, Kiyono H, Honda T.
Bacterial invasion induces interleukin-7 receptor expression
in colonic epithelial cell line, T84.
Eur J
Immunol.
1997;
27
3456-3460
MissingFormLabel
- 38
Panja A, Goldberg S, Eckmann L, Krishen P, Mayer L.
The regulation and functional consequence of proinflammatory
cytokine binding on human intestinal epithelial cells.
J
Immunol.
1998;
161
3675-3684
MissingFormLabel
- 39
Fish S M, Proujansky R, Reenstra W W.
Synergistic effects of interferon gamma and tumour necrosis
factor alpha on T84 cell
function.
Gut.
1999;
45
191-198
MissingFormLabel
- 40
Awane M, Andres P G, Li D J, Reinecker H C.
NF-kappa B-inducing kinase is a common mediator of IL-17-,
TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal
epithelial cells.
J
Immunol.
1999;
162
5337-5344
MissingFormLabel
- 41
Denning T L, Campbell N A, Song F. et al .
Expression of IL-10 receptors on epithelial cells from the
murine small and large intestine.
Int
Immunol.
2000;
12
133-139
MissingFormLabel
- 42
Dwinell M B, Eckmann L, Leopard J D, Varki N M, Kagnoff M F.
Chemokine receptor expression by human intestinal epithelial
cells.
Gastroenterology.
1999;
117
359-367
MissingFormLabel
- 43
Delezay O, Koch N, Yahi N. et al .
Co-expression of CXCR4/fusin and galactosylceramide in the
human intestinal epithelial cell line
HT-29.
Aids.
1997;
11
1311-1318
MissingFormLabel
- 44
Jordan N J, Kolios G, Abbot S E. et al .
Expression of functional CXCR4 chemokine receptors on human
colonic epithelial cells.
J Clin
Invest.
1999;
104
1061-1069
MissingFormLabel
- 45
Brumell J H, Steele-Mortimer O, Finlay B B.
Bacterial invasion: Force feeding by
Salmonella.
Curr
Biol.
1999;
9
R277-280
MissingFormLabel
- 46
Galan J E.
Salmonella interactions with host cells: type III secretion
at work.
Annu Rev Cell Dev
Biol.
2001;
17
53-86
MissingFormLabel
- 47
Kaisho T, Akira S.
Critical roles of Toll-like receptors in host
defense.
Crit Rev
Immunol.
2000;
20
393-405
MissingFormLabel
- 48
Cario E, Rosenberg I M, Brandwein S L, Beck P L, Reinecker H C, Podolsky D K.
Lipopolysaccharide activates distinct signaling pathways in
intestinal epithelial cell lines expressing Toll-like receptors.
J
Immunol.
2000;
164
966-972
MissingFormLabel
- 49
Gewirtz A T, Simon P O
Jr, Schmitt C K. et al .
Salmonella typhimurium translocates flagellin across
intestinal epithelia, inducing a proinflammatory response.
J Clin
Invest.
2001;
107
99-109
MissingFormLabel
- 50
Gewirtz A T, Navas T A, Lyons S, Godowski P J, Madara J L.
Cutting edge: bacterial flagellin activates basolaterally
expressed TLR5 to induce epithelial proinflammatory gene
expression.
J
Immunol.
2001;
167
1882-1885
MissingFormLabel
- 51
Dogan A, Wang Z D, Spencer J.
E-cadherin expression in intestinal epithelium.
J
Clin
Pathol.
1995;
48
143-146
MissingFormLabel
- 52
Huang G T, Eckmann L, Savidge T C, Kagnoff M F.
Infection of human intestinal epithelial cells with invasive
bacteria upregulates apical intercellular adhesion molecule-1 (ICAM)-1)
expression and neutrophil adhesion.
J Clin
Invest.
1996;
98
572-583
MissingFormLabel
- 53
Kvale D, Krajci P, Brandtzaeg P.
Expression and regulation of adhesion molecules ICAM-1 (CD54)
and LFA-3 (CD58) in human intestinal epithelial cell lines.
Scand J
Immunol.
1992;
35
669-676
MissingFormLabel
- 54
Morales V M, Christ A, Watt S M
et al.
Regulation of human intestinal intraepithelial lymphocyte
cytolytic function by biliary glycoprotein (CD66a).
J
Immunol.
1999;
163
1363-1370
MissingFormLabel
- 55
Parkos C A, Colgan S P, Diamond M S. et al .
Expression and polarization of intercellular adhesion
molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated
interactions with neutrophils.
Mol
Med.
1996;
2
489-505
MissingFormLabel
- 56
Yio X Y, Mayer L.
Characterization of a 180-kDa intestinal epithelial cell
membrane glycoprotein, gp180. A candidate molecule mediating t cell-epithelial
cell interactions.
J Biol
Chem.
1997;
272
12786-12792
MissingFormLabel
- 57
Kelly C P, O’Keane J C, Orellana J. et al .
Human colon cancer cells express ICAM-1 in vivo and support
LFA-1-dependent lymphocyte adhesion in vitro.
Am J
Physiol.
1992;
263
G864-870
MissingFormLabel
- 58
Elewaut D, DiDonato J A, Kim J M, Truong F, Eckmann L, Kagnoff M F.
NF-kappa B is a central regulator of the intestinal
epithelial cell innate immune response induced by infection with enteroinvasive
bacteria.
J
Immunol.
1999;
163
1457-1466
MissingFormLabel
- 59
Meijer L K, Schesser K, Wolf-Watz H, Sassone-Corsi P, Pettersson S.
The bacterial protein YopJ abrogates multiple signal
transduction pathways that converge on the transcription factor
CREB.
Cell
Microbiol.
2000;
2
231-238
MissingFormLabel
- 60
Schesser K, Spiik A K, Dukuzumuremyi J M, Neurath M F, Pettersson S, Wolf-Watz H.
The yopJ locus is required for Yersinia-mediated inhibition
of NF- kappaB activation and cytokine expression: YopJ contains a eukaryotic
SH2-like domain that is essential for its repressive activity.
Mol
Microbiol.
1998;
28
1067-1079
MissingFormLabel
Dr. med Christian Maaser
Medizinische Klinik und Poliklinik B, Westfälische
Wilhelms-Universität Münster
Albert-Schweitzer-Straße 33
48129 Münster
Email: maaser@uni-muenster.de