IL-5- and eosinophil-mediated inflammation: from discovery to therapy.
IL-5 was originally defined as a T-cell-derived cytokine that triggers activated B cells for terminal differentiation into antibody-secreting plasma cells, at least in mice. Concurrently, IL-5 was recognized as the major maturation and differentiation factor for eosinophils in mice and humans. Over-expression of IL-5 significantly increases eosinophil numbers and antibody levels in vivo. Conversely, mice lacking a functional gene for IL-5 or the IL-5 receptor alpha chain (IL-5Ralpha) display a number of developmental and functional impairments in B-cell and eosinophil lineages. In addition to the Janus kinase-signal transducer and activator of transcription pathway, the tyrosine kinases Lyn and Btk (Bruton agammaglobulinemia tyrosine kinase) are involved, and Ras GTPase-extracellular signal-regulated kinase (Ras-ERK) signals are important for IL-5-dependent cell proliferation and survival. IL-5 critically regulates expression of genes involved in proliferation, cell survival and maturation and effector functions of B cells and eosinophils. Thus, IL-5 plays a pivotal role in innate and acquired immune responses and eosinophilia. In humans, the biologic effects of IL-5 are best characterized for eosinophils. The recent expansion in our understanding of the mechanisms of eosinophil development and activation in the context of IL-5 has led to advances in therapeutic options. A new therapy currently in clinical trials uses humanized mAbs against IL-5 or the IL-5R.
Kouro
Taku
T
Laboratory of Immune Modulation, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Takatsu
Kiyoshi
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D053649:Receptors, Interleukin-5 / Q000276:immunology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D053649:Receptors, Interleukin-5