Advanced

Targeting T cell migration in inflammatory bowel disease.

Marsal, Jan LU and Agace, W W (2012) In Journal of Internal Medicine 272(5). p.411-429
Abstract
Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract, and are collectively referred to as inflammatory bowel disease (IBD). IBD is a major cause of lifetime morbidity, has a severe impact on quality of life of patients (equivalent to that of rheumatoid arthritis, asthma, migraine, or diabetes) and constitutes a substantial economic burden to the healthcare system. The introduction of anti-tumour necrosis factor antibodies has dramatically improved the treatment of IBD, but approximately one-third of patients are non-responders and another 30-50% will eventually lose the therapeutic effect or become intolerant to these antibodies. Thus there is an urgent and unmet need for new therapies.... (More)
Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract, and are collectively referred to as inflammatory bowel disease (IBD). IBD is a major cause of lifetime morbidity, has a severe impact on quality of life of patients (equivalent to that of rheumatoid arthritis, asthma, migraine, or diabetes) and constitutes a substantial economic burden to the healthcare system. The introduction of anti-tumour necrosis factor antibodies has dramatically improved the treatment of IBD, but approximately one-third of patients are non-responders and another 30-50% will eventually lose the therapeutic effect or become intolerant to these antibodies. Thus there is an urgent and unmet need for new therapies. The aetiologies of the different forms of IBD have not been fully elucidated but there is strong evidence implicating T cells and T cell migration to the gut in initiating and perpetuating the intestinal inflammatory process and tissue destruction. In recent years, progress in basic science has shed light on the mechanisms regulating T-cell migration to the gut and new therapeutics targeting these pathways have been developed. It is interesting that some of the factors directing the localization of T cells to the gut have been shown to be relatively organ specific, potentially enabling new T cell-targeted treatments to demonstrate improved safety while preserving therapeutic efficacy. Here, fundamental aspects of the gut immune system, the generation of tissue-tropic effector T cells and the mechanisms of T cell trafficking to the gut mucosa will be reviewed. In addition, the role of these processes in IBD and how they have been exploited for the development of novel therapies for IBD will be discussed. © 2012 The Association for the Publication of the Journal of Internal Medicine. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
T lymphocytes, inflammatory bowel disease, homing molecules, gastroenterology, biologics, dendritic cells
in
Journal of Internal Medicine
volume
272
issue
5
pages
411 - 429
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • wos:000310388100001
  • pmid:22946654
  • scopus:84867904783
ISSN
1365-2796
DOI
10.1111/j.1365-2796.2012.02588.x
language
English
LU publication?
yes
id
e575bd5f-e8ef-4a1e-aa43-b649a0546223 (old id 3124392)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22946654?dopt=Abstract
date added to LUP
2012-10-04 14:16:26
date last changed
2017-10-22 04:22:38
@article{e575bd5f-e8ef-4a1e-aa43-b649a0546223,
  abstract     = {Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract, and are collectively referred to as inflammatory bowel disease (IBD). IBD is a major cause of lifetime morbidity, has a severe impact on quality of life of patients (equivalent to that of rheumatoid arthritis, asthma, migraine, or diabetes) and constitutes a substantial economic burden to the healthcare system. The introduction of anti-tumour necrosis factor antibodies has dramatically improved the treatment of IBD, but approximately one-third of patients are non-responders and another 30-50% will eventually lose the therapeutic effect or become intolerant to these antibodies. Thus there is an urgent and unmet need for new therapies. The aetiologies of the different forms of IBD have not been fully elucidated but there is strong evidence implicating T cells and T cell migration to the gut in initiating and perpetuating the intestinal inflammatory process and tissue destruction. In recent years, progress in basic science has shed light on the mechanisms regulating T-cell migration to the gut and new therapeutics targeting these pathways have been developed. It is interesting that some of the factors directing the localization of T cells to the gut have been shown to be relatively organ specific, potentially enabling new T cell-targeted treatments to demonstrate improved safety while preserving therapeutic efficacy. Here, fundamental aspects of the gut immune system, the generation of tissue-tropic effector T cells and the mechanisms of T cell trafficking to the gut mucosa will be reviewed. In addition, the role of these processes in IBD and how they have been exploited for the development of novel therapies for IBD will be discussed. © 2012 The Association for the Publication of the Journal of Internal Medicine.},
  author       = {Marsal, Jan and Agace, W W},
  issn         = {1365-2796},
  keyword      = {T lymphocytes,inflammatory bowel disease,homing molecules,gastroenterology,biologics,dendritic cells},
  language     = {eng},
  number       = {5},
  pages        = {411--429},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {Targeting T cell migration in inflammatory bowel disease.},
  url          = {http://dx.doi.org/10.1111/j.1365-2796.2012.02588.x},
  volume       = {272},
  year         = {2012},
}