T cells in inflammatory bowel disease
A permanent disturbance of the balance between microbiota and immune system can lead to the development of inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Although the exact aetiology of IBD remains uncertain, the consensus is that it involves various genetic, environmental, microbial, and immune factors. Central to this aberrant response of the mucosal immune system are various inflammatory cytokines, and the therapeutic targeting of certain inflammatory molecules such as TNF-α have shown promising results. The scope of the EU-funded GUT TC PHENOTYPES (Regulation of pathogenic CD4 T cell responses in inflammatory bowel disease) project was to investigate the role of pathogenic CD4+ T cells in IBD and the molecular events that induce their activation. For this purpose, they isolated CD4+ T cells from healthy donors and IBD patients and analysed their reactivity against intestinal microbiota and pathogenic bacteria. Results showed that microbiota reactive CD4+ T cells were mainly of a memory phenotype, present in both blood and gut tissue as part of the normal human T cell repertoire. The presence of these cells did not necessarily indicate disturbed host microbiota interactions. Additionally, the consortium discovered that the cytokine oncostatin-M (OSM) and its receptor were highly expressed in IBD and promoted intestinal inflammation by activating gut-resident stromal cells. Interestingly, in an animal model of anti-TNF refractory IBD, genetic deletion or pharmacological blockade of OSM significantly attenuated colitis. OSM could thus serve as a potential biomarker and therapeutic target for IBD, with relevance for patients' refractory to anti-TNF treatment. Considering the increasing incidence of IBD and its socioeconomic burden, solid treatment solutions are urgently needed. Targeting the immunological memory that sustains intestinal inflammation, therefore, constitutes a valid novel therapeutic approach against IBD.
Keywords
Gut microbiota, inflammatory bowel disease, Crohn's disease, GUT TC PHENOTYPES, oncostatin-M