Deciphering the role of eosinophils in solid organ transplantation

Abstract

Eosinophils are rare granulocytes that belong to the innate arm of the immune system. This cell population is traditionally defined as a destructive and cytotoxic mediator in asthma and helminth infection. Limited data in transplantation have suggested that eosinophils play a similar role in potentiating deleterious organ inflammation and immunologic rejection. Contrary to this long‐held notion, recent data have uncovered the possibility that eosinophils play an alternative role in immune homeostasis, defense against a wide range of pathogens, as well as downregulation of deleterious inflammation. Specifically, translational data from small animal models of lung transplantation have demonstrated a critical role for eosinophils in the downregulation of alloimmunity. These findings shed new light on the unique immunologic features of the lung allograft and demonstrate that environmental polarization may alter the phenotype and function of leukocyte populations previously thought to be static in nature. In this review, we provide an update on eosinophils in the homeostasis of the lung as well as other solid organs.

Ischemia reperfusion injury facilitates lung allograft acceptance through IL-33-mediated activation of donor-derived IL-5 producing group 2 innate lymphoid cells

“…It is interesting that both eosinophil migration and tolerance depend on IL-5 production by ILC2s in our model. While such data support our previous demonstration that eosinophils play a dominant and non-redundant role in lung allograft acceptance, [4][5][6] we recognize that other aspects of IL-5 production and/or ILC2 activation may play a beneficial role on graft survival. For example, IL-5 can downregulate immune responses in an eosinophil-independent manner through induction of CD4 + CD25 + Foxp3 + regulatory T cells.…”

“…[60][61][62][63] Data presented here extend these findings by furthering the notion that IL-33 can facilitate allograft acceptance, albeit through an IL-5/ eosinophil-dependent mechanism that may be unique to mucosal barrier organs such as lungs. 6 T cell and eosinophil numbers, ratio, as well as the ISHLT grade of rejection were similarly increased in both ILC and IL-33 deficient compared to wild-type donor lungs, supporting the IL-33/ILC/IL-5 axis described above (Figures 4 vs. 7). Nevertheless, the histologic pattern of rejection differed somewhat allografts deficient in either ILC2s or IL-33.…”

“…5 This eosinophil/T cell "inflammatory" feedback loop is critical for long-term lung allograft survival as depletion of either cell type prevents tolerance induction. 6,7 While we have previously defined pathways controlling CD8 + T cell trafficking and differentiation in the pulmonary allograft, 7,8 mechanisms controlling eosinophil migration into the transplanted lung remain unexplored. Here, we demonstrate that ischemia reperfusion injury-mediated IL-33 production by donor-derived stromal cells facilitates eosinophil recruitment and infiltration into transplanted lung allografts.…”

Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection

“…Altogether, these data suggest that time-dependent eosinophilia is associated with immunological events and, more precisely, that transplant rejection could reflect (1) a humoral IgE response against the graft (DSA-IgE) and consecutive mast cell activation and (2) active viral infection (EBV, CMV) that activates/amplifies type 2 immunity against kidney transplantation. Though, it should be born in mind that recent studies have highlighted an immune-regulatory role of eosinophils through different mechanisms such as galectin 10 in a model of graft versus host disease [64], PD-L1 expression in response to stimulation by INF-g or by the iNOS pathway in a mice model of lung transplantation [65]. Altogether, it suggests that eosinophils could be either deleterious or protective in solid organ transplantation likely due to micro-environment but also the duration of the stimuli (acute versus chronic inflammation).…”

Immune processes in the pathogenesis of chronic lung allograft dysfunction: identifying the missing pieces of the puzzle

“…The actions of eosinophils are thought to be secondary to profibrotic features, by attracting fibroblasts and stimulating TGF-β release, as well as through toxic effects on airway epithelial cells (e.g., increased membrane permeability, ciliary damage) [84,86]. Conversely, translational data from animal models recently illustrated a role for eosinophils in the downregulation of alloimmunity, potentially by the release of suppressive molecules or interactions with dendritic cells and lymphocytes [87]. These immunosuppressive effects are presumably exerted by a different subtype of eosinophils, such as tissue-resident eosinophils, although this needs to be further elucidated [87].…”