Eosinophil Cytokines, Chemokines, and Growth Factors: Emerging Roles in Immunity

Abstract

Eosinophils derive from the bone marrow and circulate at low levels in the blood in healthy individuals. These granulated cells preferentially leave the circulation and marginate to tissues, where they are implicated in the regulation of innate and adaptive immunity. In diseases such as allergic inflammation, eosinophil numbers escalate markedly in the blood and tissues where inflammatory foci are located. Eosinophils possess a range of immunomodulatory factors that are released upon cell activation, including over 35 cytokines, growth factors, and chemokines. Unlike T and B cells, eosinophils can rapidly release cytokines within minutes in response to stimulation. While some cytokines are stored as pre-formed mediators in crystalloid granules and secretory vesicles, eosinophils are also capable of undergoing de novo synthesis and secretion of these immunological factors. Some of the molecular mechanisms that coordinate the final steps of cytokine secretion are hypothesized to involve binding of membrane fusion complexes comprised of soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs). These intracellular receptors regulate the release of granules and vesicles containing a range of secreted proteins, among which are cytokines and chemokines. Emerging evidence from both human and animal model-based research has suggested an active participation of eosinophils in several physiological/pathological processes such as immunomodulation and tissue remodeling. The observed eosinophil effector functions in health and disease implicate eosinophil cytokine secretion as a fundamental immunoregulatory process. The focus of this review is to describe the cytokines, growth factors, and chemokines that are elaborated by eosinophils, and to illustrate some of the intracellular events leading to the release of eosinophil-derived cytokines.

Regulatory T Cells Control Th2-Dominant Murine Autoimmune Gastritis

“…Eosinophils have a pathogenic role in models of allergic asthma and helminth infection (78, 79). In addition to their expansion in the stomach (Figure 4A, 4B, 5G), we also detected an increase in eosinophil percentages in the pooled lymph nodes within 2 weeks and in absolute numbers within 1 week after Treg cell depletion (Figure 6A).…”

Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

“…In combination these granules are cytotoxic and disrupt the protective pulmonary epithelial barrier allowing further inflammatory responses to occur [Frigas et al 1991]. Eosinophils have also been characterized by the ability to store preformed mediators as well as synthesize and secrete a number of pro-inflammatory cytokines, chemokines and growth factors including IL-2, IL-3, IL-4, IL-5, IL-10, IL-12, IL-13, IL-16, IL-25, tumour necrosis factor, transforming growth factor (TGF) α/β, CCL5, CCL11, 13 facilitating their key role as immunoregulators [Davoine and Lacy, 2014;Moqbel et al 1994]. …”

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“…Hypothetically, eosinophil-derived cytokines, chemokines, and growth factors may be involved in enhancing T cell-mediated tumor killing, particularly at the level of the local tissue environment where large numbers of infiltrating eosinophils accumulate and are actively degranulating onto tumor cells [35].…”