Title:Interleukin-7: a key Mediator in T Cell-driven Autoimmunity, Inflammation, and Tissue Destruction
Volume: 18
Issue: 16
Author(s): Angela Bikker, C. Erik Hack, Floris P.J.G. Lafeber and Joel A.G. van Roon
Affiliation:
Keywords:
IL-7, IL-7 receptor, immunopathology, T cells, macrophages, rheumatic diseases, inflammatory disorders, autoimmunity
Abstract: IL-7, expressed by stromal cells in primary lymphoid organs, is known for its critical role in the development and homeostatic
expansion of T cells in humans and mice. IL-7 is equally important for B cell development in human and mice, but only in mice seems
critical for B cell development and expansion. Recent studies demonstrate that this potent immunostimulatory cytokine is overexpressed
in inflamed tissues of patients with (rheumatic) autoimmune diseases and that expression levels correlate with clinical parameters of disease.
In inflamed tissues several cell types, including macrophages, dendritic cells, and fibroblasts produce IL-7. IL-7 primarily acts on T
cells that abundantly express the IL-7 receptor and that are increased at the inflammatory sites, and predominantly induces Th1 and
Th17-associated cytokine secretion. IL-7-mediated T cell-dependent activation of macrophages, dendritic cells and B cells is accompanied
by up regulation of T cell differentiating factors, chemokines, adhesion/co-stimulatory molecules and catabolic cytokines and enzymes.
Moreover, overexpression of IL-7 is associated with ectopic lymphoid aggregate formation, corresponding with the capacity of
IL-7 to induce LTβ and TNFα and to activate innate lymphoid tissue inducer cells. Additionally, IL-7 promotes T cell-driven osteoclastogenesis
and fibroblast activation, processes involved in tissue destruction in chronic inflammation. Altogether this suggests that IL-7 is
an important proinflammatory mediator in several chronic (rheumatic) inflammatory autoimmune diseases. The substantial amelioration
of inflammation and immunopathology in experimental animal models for these diseases by blocking IL-7(receptor) supports this role of
IL-7 and demonstrates that IL-7 and its receptor represent novel targets for immunotherapy.
