Eosinophils in mucosal immune responses

Abstract

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells.

Lung-resident eosinophils represent a distinct regulatory eosinophil subset

“…Under basal conditions, most eosinophils reside in the tissue where they exert key homeostatic functions (1,2,8,16). Microarray analyses revealed that lung rEos specifically expressed several genes, such as Anxa1 (46), Nedd4 (47), Runx3 (48), Serpinb1a (49), and Ldlr (50), that are involved in the maintenance of lung immune homeostasis.…”

“…By contrast, eosinophilopoiesis is dramatically increased as a result of Th2 cell responses associated with helminth infections or allergic diseases such as asthma (1,2,8). This increase in eosinophil production is driven by a dedicated set of cytokines, namely IL-3, IL-5, and granulocyte macrophage-CSF (GM-CSF) (1,8).…”

“…iEos showed higher In fact, under baseline conditions, eosinophils rapidly leave the bloodstream to enter tissues, mainly the gastrointestinal tract, adipose tissue, thymus, uterus, and mammary glands, where they regulate a variety of important biological functions (1,2,8,16). The vast majority of these tissue-resident eosinophils (rEos) are found in the nonesophageal portions of the gastrointestinal tract, where they promote IgA class switching and the maintenance of IgA-expressing plasma cells (17,18).…”

“…Lung-resident eosinophils represent a distinct regulatory eosinophil subset Claire Mesnil, 1,2 Stéfanie Raulier, 1 Geneviève Paulissen, 1 Xue Xiao, 2,3 Mark A. Birrell, 4 Dimitri Pirottin, 1,2 Thibaut Janss, 1 Philipp Starkl, 5 Eve Ramery, 2 Monique Henket, 6,7 Florence N. Schleich, 6,7 Marc Radermecker, 8 Kris Thielemans, 9 Laurent Gillet, 2,3 Marc Thiry, 10 Maria G. Belvisi, 4 Renaud Louis, 6,7 Christophe Desmet, 1,2 Thomas Marichal, 1,2 and Fabrice Bureau plemental Figure 2), suggesting that they were undergoing piecemeal degranulation, a process during which granule proteins are released gradually (34,35). Some low-density granules displayed a central structure that most likely corresponded to the central MBP-containing core typical of eosinophil granules (34,35), and contained intragranular vesiculotubular structures previously delineated within human eosinophilic granules (35) (Supplemental Figure 2, arrows and arrowheads, respectively).…”

“…Eosinophils are terminally differentiated granulocytes that develop in the BM under the control of key transcription factors, mainly GATA1, C/EBPα, PU.1, and XBP1 (1)(2)(3)(4)(5)(6). They are characterized by the presence in their cytoplasm of specific secondary granules containing toxic cationic proteins, which are stainable with acid aniline dyes and Congo red (1,7).…”