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

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.

Group 2 Innate Lymphoid Cells Promote an Early Antibody Response to a Respiratory Antigen in Mice

“…Our finding that ILC2s promote anti-CD40-induced IgM or IgG1 production only in the presence of exogenous IL-4 (Figure 2A) suggests that ILC2-derived IL-4 is unlikely to be sufficient to upregulate Ig production in this experimental setting. IL-5 is another important cytokine that regulates B cell growth and antibody production (29). Indeed, mice deficient in IL-5Rα showed decreased numbers of B1 cells in the peritoneal cavity and decreased serum levels of IgM, but not IgG1 (29, 30).…”

Low eosinophil and low lymphocyte counts and the incidence of 12 cardiovascular diseases: a CALIBER cohort study

“…Another potential explanation is that high levels of endogenous mineralocorticoids increase the risk of heart failure via sodium retention, and also suppress eosinophil and lymphocyte counts (adrenal insufficiency may be associated with eosinophilia38 and lymphocytosis39). A third explanation involves interleukin-5 (IL-5), which mediates the release of eosinophils into the bloodstream40 and is involved in differentiation of B lymphocytes to immunoglobulin-secreting cells 41. Variants in the IL-5 gene are associated with coronary artery disease,42 and in mouse studies macrophage-specific overexpression of IL-5 led to increased secretion of IgM antibodies that inhibit uptake of oxidised low-density lipoprotein, with consequent inhibition of atherosclerosis 43.…”

Prolonged activation of IL-5–producing ILC2 causes pulmonary arterial hypertrophy

“…+ T helper type 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s), and is particularly important in eosinophil biology (1,2). We and others have reported that the majority of IL-5-producing cells in the lung or intestine of naive or IL-33-treated mice were ILC2s, and they were responsible for maintaining and regulating eosinophils (3)(4)(5)(6).…”