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- Marsal, Jan, et al.
(författare)
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Targeting T cell migration in inflammatory bowel disease.
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 272:5, s. 411-429
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Tidskriftsartikel (refereegranskat)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.
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