International Immunology Advance Access originally published online on October 9, 2009
International Immunology 2009 21(12):1303-1309; doi:10.1093/intimm/dxp102
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review-article |
IL-5- and eosinophil-mediated inflammation: from discovery to therapy
1 Laboratory of Immune Modulation, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan
2 Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan
3 Toyama Prefectural Institute of Pharmaceutical Research, 17-1 Naka-Taikoyama, Imizu-shi, Toyama 939-0363, Japan
Correspondence to: K. Takatsu; E-mail: takatsuk{at}med.u-toyama.ac.jp
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-5R
) 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.
Keywords: airway, B cell, cytokine, eosinophil, Th1/Th2
Received 7 August 2009, accepted 18 September 2009.