Affecting over 500,000 people in the UK, IBD comprises Crohn’s disease and ulcerative colitis
The study, published in Nature Immunology, could help identify new ways to treat inflammatory bowel disease (IBD).
Collectively known as IBD, Crohn’s disease and ulcerative colitis are incurable conditions that involve excessive inflammation in the gut and affect over 500,000 people in the UK, according to Crohn’s & Colitis UK.
In this study, researchers deleted two proteins, c-Maf and Blimp-1, from T cells in mice to understand their role in maintaining gut health via IL-10.
Mutations in the cytokine IL-10 or its receptor can result in IBD in children and it has previously been shown that c-Maf and Blimp-1 can drive the activity of the IL-10 gene in T cells.
They found that, when combined with an environmental trigger – an infection with the Helicobacter hepaticus bacterium – IL-10 activity in T cells was reduced and inflammation progressed.
After 14 days, researchers revealed that when either c-Maf or Blimp-1 was missing, moderate colitis was induced and severe colitis occurred in mice when both proteins were removed.
Additionally, results showed that the proteins were protective against inflammation on IL-10, acting through different immune pathways that impact T cell activities.
After studying colon biopsies of patients with IBD, researchers found similarities in the genes expressed in humans and mice with bacteria-induced inflammation resulting from the absence of c-Maf or Blimp-1.
The team plans to investigate how intestinal inflammation can develop and progress to colitis in response to different microorganisms.
Anne O’Garra, head of the Immunoregulation and Infection Laboratory, the Crick, commented: “Our findings show that Blimp-1 and c-Maf not only co-operate to regulate IL-10 expression to prevent severe bacteria-induced colitis but reinforce this control by their distinct actions on distinct inflammatory T cell molecules.
“We hope that these studies will enable further dissection of the roles of key genes and pathways relevant to IBD in humans.”