The dual role of TNF in inflammation and tissue repair

Targeting the cytokine tumour necrosis factor (TNF) has revolutionised the treatment of chronic inflammatory diseases. In Inflammatory Bowel Disease (IBD), targeting TNF does not only dampen the inflammation, but also induces tissue repair mechanisms. Research of Andrey Kruglov´s group at the DFRZ, now published in Mucosal Immunology, has unraveled the mechanisms involved.

In a humanised mouse model of IBD they showed that TNF induces a soluble antagonist (IL-22Ra2; IL-22BP) of the cytokine interleukin-22, thus blocking this key cytokine of tissue repair. Interestingly, while T cell-derived TNF did perpetuate inflammation by recruiting inflammatory cells to the intestine, TNF produced by epithelial cells did induce IL-22BP expression, inhibiting tissue repair. Understanding this division of labour of TNF-producing cells has implications beyond IBD, for other chronic inflammatory rheumatic diseases. It offers entirely new options for precise therapeutic targeting of distinct functions of multifunctional cytokines, like TNF.