FAM26F protein: Innate regulator of Type 3 immune responses

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Breakdown in the balance between tolerance to harmless commensal bacteria and protection against pathogens leads to intestinal inflammation and development of inflammatory bowel disease (IBD), which is the common name for ulcerative colitis (UC) and Crohn's disease (CD). IBD affects approximately 1 in every 250 people in the UK. Current treatments (surgery or immunosuppression/immunomodulation) are not always effective and may cause serious side effects. Thus, new therapies are needed, but rational development of such therapies requires new target identification and validation. Recent genome-wide association studies (GWAS) have linked several gene polymorphisms with UC. Amongst these is one in the regulatory region of a newly described gene called FAM26F (Family with sequence similarity 26, member F). FAM26F expression is increased in the mucosa of patients with active UC compared to healthy controls. FAM26F also predicts the outcome of corticosteroid therapy in rheumatoid arthritis (RA), the therapy that is also used to treat UC patients. To understand FAM26F function, we have generated FAM26F-deficient mice and found that FAM26F controls the induction of inflammatory cytokines, which are associated with UC disease progression, and instruction of T helper (Th17) T cell responses. We now seek support to elucidate the mechanism of FAM26F function and its clinical significance, using UC as a model. We have also identified FAM26F-deficient humans, which will allow us to directly translate findings made in mice to humans. Achieving these objectives will generate new therapeutic targets and/or biomarkers needed to better manage and treat UC or other Th17-linked diseases.