Homeostatic Eosinophils: Characteristics and Functions

Abstract

Eosinophils are typically considered to be specialized effector cells that are recruited to the tissues as a result of T helper type 2 (Th2) cell responses associated with helminth infections or allergic diseases such as asthma. Once at the site of injury, eosinophils release their cytotoxic granule proteins as well as preformed cytokines and lipid mediators, contributing to parasite destruction but also to exacerbation of inflammation and tissue damage. Accumulating evidence indicates that, besides their roles in Th2 responses, eosinophils also regulate homeostatic processes at steady state, thereby challenging the exclusive paradigm of the eosinophil as a destructive and inflammatory cell. Indeed, under baseline conditions, eosinophils rapidly leave the bloodstream to enter tissues, mainly the gastrointestinal tract, lungs, adipose tissue, thymus, uterus, and mammary glands, where they regulate a variety of important biological functions, such as immunoregulation, control of glucose homeostasis, protection against obesity, regulation of mammary gland development, and preparation of the uterus for pregnancy. This article provides an overview of the characteristics and functions of these homeostatic eosinophils.

Keywords: eosinophils; homeostasis; immunomodulation; innate immunity; mucosae.

Figure 1

Schematic overview of the origin, interleukin (IL)-5 dependence, phenotype, and functions of homeostatic eosinophils (hEos) in mice. hEos are produced in the bone marrow from the EoP precursor independently of IL-5. Conversely, inflammatory eosinophils (iEos) require IL-5 for their production. hEos are uniformly characterized by expression of Siglec-F, F4/80, CD125, and CCR3. hEos transit through the blood circulation to home into tissues at baseline. Blood hEos have a ring-shaped nucleus and express CD62L, while iEos have a segmented nucleus and do not express CD62L but express CD101. hEos homing to the tissues is either dependent (dark red) or independent (white) on IL-5. The IL-5-(in)dependence of thymic and mammary gland hEos remains unknown. Tissue hEos display distinct phenotype, half-life (T_1/2), and homeostatic functions. The surface phenotype depicted shows whether hEos express (colored symbols) or do not express (white symbols) the indicated surface markers. When marker expression is undefined, the symbol is not present. The function described in italic has been suggested, but a clear demonstration is still lacking. h, hours.