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Cytokine. 2017 Oct;98:59-70. doi: 10.1016/j.cyto.2016.11.011.

Allergic diseases: From bench to clinic - Contribution of the discovery of interleukin-5.

Author information

1
Toyama Prefectural Institute of Pharmaceutical Research, 17-1 Nakataikouyama, Imizu City, Toyama 939-0363, Japan; Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
2
Kyowa Hakko Kirin Co., Ltd., Otemachi Finamcial City Grand Cube, 1-9-2, Chiyoda-ku, Tokyo 100-8185, Japan.
3
Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan; JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
4
Toyama Prefectural Institute of Pharmaceutical Research, 17-1 Nakataikouyama, Imizu City, Toyama 939-0363, Japan; Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. Electronic address: takatsuk@med.u-toyama.ac.jp.

Abstract

T helper 2 cells produce a number of cytokines including inteleukin (IL)-5, IL-4 and IL-13. Group 2 innate lymphoid cells (ILC2s) also produce IL-5 under sterile conditions. IL-5 is interdigitating homodimeric glycoprotein and a member of the four α helical bundle motifs conserved among hematopoietic cytokines. IL-5 exerts its effects on target cells via IL-5 receptor (IL-5R), composed of an IL-5R α and βc subunit. The membrane proximal proline-rich motif of the cytoplasmic domain of both IL-5R α and βc subunits is essential for IL-5 signal transduction. Although IL-5 was initially identified by its ability to support the growth and terminal differentiation of mouse B cells into antibody-secreting cells, recombinant IL-5 exerts pleiotropic activities on various target cells. For example, IL-5 is now recognized as the major maturation and differentiation factor for eosinophils in mice and humans. Overexpression of IL-5 in mouse significantly increases eosinophil numbers and antibody levels in vivo, while mice lacking a functional gene for IL-5 or IL-5R display developmental and functional impairments in B cell and eosinophil lineages. In mice, the role of the IL-5/IL-5R system in the production and secretion of Immunoglobulin (Ig) M and IgA in mucosal tissues has been reported. Although eosinophils protect against invading pathogens including virus, bacteria and helminthes, they are also involved in the pathogenesis of various diseases, such as food allergy, asthma, and inflammatory bowel diseases. The recent expansion in our understanding in the context of IL-5 and IL-5-producing ILC2s in eosinophil activation and the pathogenesis of eosinophil-dependent inflammatory diseases has led to advances in therapeutic options. A new therapy currently under invetigarion in clinical trials uses humanized monoclonal antibodies against IL-5 or the IL-5R. In this review, we summarize our current understanding of the functions of IL-5 and its receptor, the innate regulation of IL-5-producing cells, and therapeutic potential of anti-IL-5 and anti-eosinophil (IL-5R) antibodies.

KEYWORDS:

Allergy; Benralizumab; Eosinophil; ILC2; Mepolizumab/Reslizumab; Severe asthma; Th2

PMID:
28863833
DOI:
10.1016/j.cyto.2016.11.011
[Indexed for MEDLINE]

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