Targeting T‐cell migration in inflammatory bowel disease

Abstract

Abstract. Marsal J, Agace WW

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

“…A recent review evaluated the safety and efficacy of vedolizumab for the treatment of CD, and it was concluded that vedolizumab is an effective and well-tolerated drug [287]. Though it does not increase the risk of infection, it was demonstrated that vedolizumab may reduce the number of Treg cells and consequently their suppressive effect on colonic inflammation (see review [288]). …”

The Histopathologic Spectrum of Kidney Biopsies in Patients with Inflammatory Bowel Disease

“…The two most common types are Crohn disease (CD) and ulcerative colitis (UC). The inciting agent and exact underlying mechanism of IBD are not entirely known; however, convincing evidence suggests that it is mediated by abnormal T cell function in genetically susceptible individuals (1,2). Extraintestinal manifestations of IBD are not uncommon and probably reflect systemic inflammation, autoimmune susceptibility, metabolic and nutritional derangement, or drug-related toxicity (3,4).…”

Lymphocyte Trafficking to Mucosal Tissues

“…However, perhaps because of antagonizing α4β1, which mediates lymphocyte homing into the brain (Haanstra et al, 2013), natalizumab was associated with an increased risk of progressive multifocal leukoencephalopathy (Clifford et al, 2010). In contrast, this serious adverse event has not been reported in subjects receiving therapeutic modalities that specifically target T cell gut homing for the treatment of IBD (Marsal and Agace, 2012). These therapies include vedolizumab, a humanized antibody specific for the α4β7 dimer ( Feagan et al, , 2008; PF-00547-659, a fully human antibody against MAdCAM-1 ; etrolizumab, a humanized antibody against integrin subunit β7 (Marsal and Agace, 2012); and a small molecule CCR9 antagonist (CCX282, traficet-EN) (Keshav et al, 2013;Villablanca et al, 2011a).…”

“…IBD might develop as a result of exaggerated T cell responses or inadequate regulatory pathways. Consistent with this view point, polymorphisms in IL-23R, STAT3, IL-21, IL-2, IL-2R, IL-7R, IL-10, and JAK2 loci (Khor et al, 2011) have been associated with IBD (Marsal and Agace, 2012).…”

“…The number of T cells, especially CD4 + T cells, is increased in the mucosa of IBD patients (Sturm et al, 2008), and T cells are thought to contribute to the pathogenesis of IBD (Marsal and Agace, 2012). T cells reactive to specific enteric bacteria can transfer experimental colitis from one animal to another (Cong et al, 1998;Kullberg et al, 2003), and adoptive transfer of CD4 + or CD8 + T N cells to recombination activation gene-deficient mice leads to colitis (Powrie et al, 1993(Powrie et al, , 1994Tajima et al, 2008).…”