Origins and functions of eosinophils in two non-mucosal tissues

Abstract

Eosinophils are a type of granulocyte named after the presence of their eosin-stained granules. Traditionally, eosinophils have been best known to play prominent roles in anti-parasitic responses and mediating allergic reactions. Knowledge of their behaviour has expanded with time, and they are now recognized to play integral parts in the homeostasis of gastrointestinal, respiratory, skeletal muscle, adipose, and connective tissue systems. As such, they are implicated in a myriad of pathologies, and have been the target of several medical therapies. This review focuses on the lifespan of eosinophils, from their origins in the bone marrow, to their tissue-resident role. In particular, we wish to highlight the functions of eosinophils in non-mucosal tissues with skeletal muscle and the adipose tissues as examples, and to discuss the current understanding of their participation in diseased states in these tissues.

Keywords: adipose tissue; eosinophil; immune cells; skeletal muscle; tissue repair.

Figure 1

Eosinophils are present in most -if not all- type of tissues. Once fully differentiated, eosinophils exit the bone marrow, enter and patrol the circulation. Upon stimulation (damage, cytokine/chemokine gradient), they migrate to various tissues where they home into the interstitial space and, with the support of other immune cells, provide a Th2 micro-environment that will participate to maintain tissue homeostasis. Eosinophils predominate within the lamina propria of the gastrointestinal tract; the lung parenchyma; the cortico-medullary region of the thymus; the bulbous end of developing terminal end buds of mammary glands; the endometrium of the uterus; and finally, within the interstitial space of the adipose tissue and skeletal muscle. Figure adapted from Marichal et al. (10).

Figure 2

Hierarchical tree of eosinophil progenitor formation in the bone marrow. The common myeloid progenitor (CMP) give rise to both megakaryocyte Erythrocytes Progenitors (MEP) and Granulocyte monocyte progenitor (GMP). The latest then produce the eosinophil progenitors thanks to various chemokines such as GM-CSF, IL-3, and IL-5. Later on, these cells down-regulate CD34 and leave the bone marrow for the circulation.

Figure 3

Eosinophil and muscle repair Top: After an injury, eosinophils are attracted to the site of damage via the production of CCL11 and IL-5. They then secrete various cytokine and in particular IL-4, which will support FAP trophic function toward myogenic cells. Bottom: In case of chronic injury, such as seen in dystrophic muscle, eosinophil will degranulate Major basic protein 1 will be released in the environment, lysing myofibers, participating into the degenerative phenotype.

Figure 4

The role of eosinophils in adipose tissue homeostasis. (A) Adipose tissue is composed of a rich network of adipocytes, stromal cells and immune cells. In adipose tissue homeostasis, the eosinophil population is maintained by signals from mesenchymal stromal cells and ILC2s. Eosinophil-secreted IL-4 and IL-13 maintains alternatively activated macrophage polarization, which produce catecholamines that promote thermogenesis via the biogenesis of beige adipocytes. (B) Major inflammatory cells in lean and obese states. AAM, alternatively activated macrophages; CCL11, eotaxin-1; IL, interleukin; ILC2, Type 2 innate lymphoid cell; IFNγ, interferon gamma; Met-Enk, Met-enkephalin; NK, natural killer cells; TNFα, tumour necrosis factor alpha; TGF-β, transforming growth factor beta.