Interleukin-5 and IL-5 receptor in health and diseases

Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
Proceedings of the Japan Academy Ser B Physical and Biological Sciences (Impact Factor: 2.56). 10/2011; 87(8):463-85. DOI: 10.2183/pjab.87.463
Source: PubMed

ABSTRACT While interleukin-5 (IL-5) is initially identified by its ability to support the growth and terminal differentiation of mouse B cells in vitro into antibody-secreting cells, recombinant IL-5 exerts pleiotropic activities on various target cells including B cells, eosinophils, and basophils. IL-5 is produced by both hematopoietic and non-hematopoietic cells including T cells, granulocytes, and natural helper cells. IL-5 exerts its effects for proliferation and differentiation via receptors that comprise an IL-5-specific α and common β-subunit. IL-5Rα expression in activated B cells is regulated by a complex of transcription factors including E12, E47, Sp1, c/EBPβ, and Oct2. IL-5 signals are transduced through JAK-STAT, Btk, and Ras/Raf-ERK signaling pathways and lead to maintenance of survival and functions of B cells and eosinophils. Overexpression of IL-5 in vivo significantly increases eosinophils and B cells in number, while mice lacking a functional gene for IL-5 or IL-5 receptor display a number of developmental and functional impairments in B cells and eosinophil lineages. In humans, the biologic effects of IL-5 are best characterized for eosinophils. The recent expansion in our understanding of eosinophil development and activation and pathogenesis of eosinophil-dependent inflammatory diseases has led to advance in therapeutic options. Intravenous administration of humanized anti-IL-5 monoclonal antibody reduces baseline bronchial mucosal eosinophils in mild asthma; providing important implications for strategies that inhibit the actions of IL-5 to treat asthma and other allergic diseases.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Atherosclerosis 12/2014; 239(1):125-130. DOI:10.1016/j.atherosclerosis.2014.12.046 · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the lung is the most common metastatic site for cancer cells, biological mechanisms regulating lung metastasis are not fully understood. Using heterotopic and intravenous injection models of lung metastasis in mice, we found that IL-5, a cytokine involved in allergic and infectious diseases, facilitates metastatic colonization through recruitment of sentinel eosinophils and regulation of other inflammatory/immune cells in the microenvironment of the distal lung. Genetic IL-5 deficiency offered marked protection of the lungs from metastasis of different types of tumor cells, including lung cancer, melanoma and colon cancer. IL-5 neutralization protected subjects from metastasis, whereas IL-5 reconstitution or adoptive transfer of eosinophils into IL-5 deficient mice exerted pro-metastatic effects. However, IL-5 deficiency did not affect the growth of the primary tumor or the size of metastatic lesions. Mechanistic investigations revealed that eosinophils produce CCL22, which recruits regulatory T cells (Treg) to the lungs. During early stages of metastasis Treg created a pro-tumorigenic microenvironment, potentially by suppressing IFNγ-producing natural killer cells and M1-polarized macrophages. Together, our results establish a network of allergic inflammatory circuitry that can be co-opted by metastatic cancer cells to facilitate lung colonization, suggesting interventions to target this pathway may offer therapeutic benefits to prevent or treat lung metastasis. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 02/2015; DOI:10.1158/0008-5472.CAN-14-2379 · 9.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies correlate vitamin D deficiency with asthma severity. Calcitriol modulates receptor and cytokine expression from various leukocytes in an anti-inflammatory manner. Despite eosinophil activity during mucosal inflammation, knowledge on the direct effect of calcitriol on this granulocyte is very limited. We propose that calcitriol exerts direct effects on eosinophil biology by modulating its programmed cell death pathways and other functions. Purified peripheral blood eosinophils from atopic donors were incubated with calcitriol (10nM) for up to 14 days with and without IL-5. We observed that calcitriol significantly reduced eosinophil necrosis and cytolytic release of EPX in media when co-incubated with IL-5. The addition of calcitriol also significantly decreased CRTh2 and CCR10 expression on eosinophils. Eosinophil cytotoxic mediator release into mucosal tissues, resulting from necrotic cytolysis, as well as eosinophil recruitment to lungs are major contributors to airway inflammation in allergic asthma. Hence, the reduction of mucosal inflammation achieved by decreasing eosinophil necrosis and recruitment unveil new anti-inflammatory mechanisms for calcitriol in the context of airway inflammation.
    08/2014, Degree: Master of Science in Experimental Medicine, Supervisor: Francis Davoine

Full-text (2 Sources)

Available from
May 29, 2014