The role of interleukin-15 in the spectrum of inflammatory diseases

Interleukin-15 (IL-15) is a pleiotropic, pro-inflammatory cytokine, constitutively expressed in both hematopoietic and non-hematopoietic cells. The role of IL-15 during systemic inflammatory diseases, including autoimmune and autoinflammatory disorders, is to be fully clarified yet. Due to its effects on immune cells, IL-15 has attracted attention as a potential new therapeutic target for modulating immune responses, either by enhancing immune surveillance or by controlling excessive inflammation.

We provided a landscape about IL-15 in systemic inflammatory diseases, from its biological functions to the possible mechanistic roles, using rheumatoid arthritis (RA) and Still's disease as autoimmune and autoinflammatory models, respectively.

IL-15 exerts its pathogenetic activity by the induction of a deregulated activation of innate and adaptive arms of the immune system, at the crossroad of autoimmune and autoinflammatory disorders. During RA, IL-15 mediates the production from T cells and macrophages of TNF, which may induce further production of IL-15 by synoviocytes via a vicious pathogenic loop. During Still's disease, together with IFN-I, IL-15 promotes the expansion of NK cells and of CD38+HLA-DR+ T cells, which are highly activated in disease life-threatening evolution. Thus, novel IL-15-targeted therapeutic strategies could be explored to improve the management of systemic inflammatory diseases.