Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

I. H. Hiemstra; E. J. Klaver; K. Vrijland; Helene Kringel; Annette Andreasen; G. Bouma; G. Kraal; I. van Die; J. M. M. den Haan

doi:10.1016/j.molimm.2014.03.003

Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

I. H. Hiemstra, E. J. Klaver, K. Vrijland, Helene Kringel, Annette Andreasen, G. Bouma, G. Kraal, I. van Die, J. M. M. den Haan

33 Citations (Scopus)

Abstract

The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.

Original language	English
Journal	Molecular Immunology
Volume	60
Issue number	1
Pages (from-to)	1-7
Number of pages	7
ISSN	0161-5890
DOIs	https://doi.org/10.1016/j.molimm.2014.03.003
Publication status	Published - Jul 2014

Keywords

Animals
Biological Transport
Cell Line
Chemokine CXCL1
Claudin-4
Crohn Disease
Cytokines
Dendritic Cells
Helminth Proteins
Humans
Intestinal Mucosa
Lipopolysaccharides
Mice
Neoplasm Proteins
Polysaccharides
Receptors, Cell Surface
Th2 Cells
Therapy with Helminths
Tight Junctions
Trichuris
Tumor Necrosis Factor-alpha

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10.1016/j.molimm.2014.03.003

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title = "Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells",

abstract = "The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.",

keywords = "Animals, Biological Transport, Cell Line, Chemokine CXCL1, Claudin-4, Crohn Disease, Cytokines, Dendritic Cells, Helminth Proteins, Humans, Intestinal Mucosa, Lipopolysaccharides, Mice, Neoplasm Proteins, Polysaccharides, Receptors, Cell Surface, Th2 Cells, Therapy with Helminths, Tight Junctions, Trichuris, Tumor Necrosis Factor-alpha",

author = "Hiemstra, {I. H.} and Klaver, {E. J.} and K. Vrijland and Helene Kringel and Annette Andreasen and G. Bouma and G. Kraal and Die, {I. van} and Haan, {J. M. M. den}",

year = "2014",

month = jul,

doi = "10.1016/j.molimm.2014.03.003",

language = "English",

volume = "60",

pages = "1--7",

journal = "Molecular Immunology",

issn = "0161-5890",

publisher = "Pergamon Press",

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T1 - Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

AU - Hiemstra, I. H.

AU - Klaver, E. J.

AU - Vrijland, K.

AU - Kringel, Helene

AU - Andreasen, Annette

AU - Bouma, G.

AU - Kraal, G.

AU - Die, I. van

AU - Haan, J. M. M. den

PY - 2014/7

Y1 - 2014/7

N2 - The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.

AB - The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.

KW - Animals

KW - Biological Transport

KW - Cell Line

KW - Chemokine CXCL1

KW - Claudin-4

KW - Crohn Disease

KW - Cytokines

KW - Dendritic Cells

KW - Helminth Proteins

KW - Humans

KW - Intestinal Mucosa

KW - Lipopolysaccharides

KW - Mice

KW - Neoplasm Proteins

KW - Polysaccharides

KW - Receptors, Cell Surface

KW - Th2 Cells

KW - Therapy with Helminths

KW - Tight Junctions

KW - Trichuris

KW - Tumor Necrosis Factor-alpha

U2 - 10.1016/j.molimm.2014.03.003

DO - 10.1016/j.molimm.2014.03.003

M3 - Journal article

C2 - 24705296

SN - 0161-5890

VL - 60

SP - 1

EP - 7

JO - Molecular Immunology

JF - Molecular Immunology

IS - 1

ER -

Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

Abstract

Keywords

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