Inflammatory bowel diseases like Crohn's disease and ulcerative colitis manifest with chronic inflammation in the gastrointestinal tract. Current treatment mainly entails the administration of immunosuppressive drugs, inhibition of the tumour necrosis factor and, in extreme cases, surgical removal of the affected part of the intestine. The team behind the EU-funded 'Innate lymphoid cells in intestinal homeostasis and immunity' (ILCHI) project wished to delineate how inflammation leads to such pathological conditions. Their work focused on the role of nuclear hormone receptor RORγt, a surface antigen present on pro-inflammatory cells. These RORγt-expressing innate lymphoid cells (ILC3s) are required for the development of lymphoid tissues, for the interaction with symbiotic microbiota, and are implicated in the defence against pathogens. There is a reciprocal regulation between symbiotic bacteria and ILC3s, leading to a fine equilibrium between the host and the symbionts. The scope of the ILCHI study was to delineate the mechanism underlying this crosstalk. To this end, scientists screened mice with deletions in one of the innate immune pathways and also looked at the impact of various cytokines. Different immune cells imposed a different function on ILC3s, illustrating the complexity of ILC3 regulation. For this purpose, researchers generated a new transgenic mouse harbouring a specific and timely deletion of ILC3s. This is expected to provide key data on the role of ILC3s in immune system development, on the symbiotic microbiota and on inflammatory pathologies. The generated information will support the development of novel treatment modalities based on re-establishing intestinal homeostasis rather than blocking pro-inflammatory immunity. In view of the recent association between the loss of intestinal homeostasis and the onset of autoimmunity in distant organs, ILCHI findings could be extrapolated for other autoimmune disturbances.
Intestinal homeostasis, inflammation, inflammatory bowel diseases, intestine, innate lymphoid cells, RORγt, ILC3