Cells (Feb 2025)
Humanized FcεRI Expressed on Mouse Eosinophils Mediates IgE-Facilitated Eosinophil Antigen Presentation
Abstract
High-affinity IgE receptors (FcεRI) are expressed on human blood eosinophils and may be upregulated on eosinophils at sites of allergic inflammation including atopic dermatitis and allergic asthma. FcεRI engagement, however, fails to elicit “effector” responses from eosinophils. Thus, a functional role for FcεRI on eosinophils has been uncertain. We evaluated the role of FcεRI in enhancing eosinophil antigen presentation in vivo by using humanized FcεRI α chain (hFcεRIα) transgenic mice. Eosinophils from hFcεRIα transgenic mice expressed humanized FcεRIα, with higher levels of eosinophils from the bronchoalveolar lavage of experimental asthma than those from polymyxin-elicited peritoneal lavage. The hFcεRIα-bearing eosinophils instilled intratracheally (i.t.) into recipient wild-type mice migrated from airways into paratracheal lymph nodes (pLNs) and spleens. Eosinophils, pretreated in vitro with nitrophenyl-ovalbumin ((NP)-OVA) and anti-NP human IgE complexes and instilled i.t., presented NP antigen via hFcεRIα to T cells more effectively than those pretreated with NP-OVA only, as assessed by pLN cell proliferation. IgE/FcεRIα-facilitated eosinophil antigen presentation resulted in increased IL-4 but not INF-γ production by pLN cells, with a bias towards Th2 cytokine production. Furthermore, cross-linking hFcεRIα on eosinophils increased eosinophil expressions of T cell costimulatory proteins CD40, CD80, and CD86. Humanized FcεRIα on murine eosinophils functions to enhance eosinophil antigen presentation capacities by mediating IgE-facilitated antigen presentation and upregulating expression of requisite T cell costimulatory proteins. Thus, a functional, non-“effector” role for FcεRI on eosinophils is revealed through identifying a means by which IgE may act on eosinophils to mediate their immunomodulatory, enhanced antigen presentation capabilities.
Keywords
