Abstract
Eosinophils are major effector cells during allergic responses and helminth infections. Recent studies further highlight eosinophils as important players in many other biological processes. Therefore it is important to understand how these cells can be modulated in terms of survival and effector function. In the present study we investigated how eosinophils respond to the alarmin IL-33. We show that IL-33 promotes eosinophil survival in a ST2- and MyD88-dependent manner. IL-33-mediated protection from apoptosis was dependent on autocrine GM-CSF release. In addition, GM-CSF increased the IL-33-induced secretion of IL-4 and IL-13 from eosinophils. Unexpectedly, this effect was further enhanced by cross-linking of Siglec-F, a proposed inhibitory and apopotosis-inducing receptor on eosinophils. Co-culture experiments with eosinophils and macrophages revealed that the IL-33-induced release of IL-4 and IL-13 from eosinophils was required for differentiation of alternatively activated macrophages (AAMs). The differentiation of AAMs could be further increased in the presence of GM-CSF. These results indicate that cross-talk between Siglec-F and the receptors for IL-33, LPS and GM-CSF plays an important role for efficient secretion of IL-4 and IL-13. Deciphering the molecular details of this cross-talk could lead to the development of new therapeutic option to treat eosinophil-associated diseases.
Highlights
The alarmin IL-33 is a member of the IL-1 family which is rapidly released during tissue damage and serves as an important mediator of barrier immunity in skin, lung and intestine [1]
These results indicate that cross-talk between Siglec-F and the receptors for IL-33, LPS and GM-CSF plays an important role for efficient secretion of IL-4 and IL-13
Eosinophils were cultured in the absence of IL-5 but in the presence of 10 ng/ml IL-33 to investigate whether IL-33 protects from spontaneous apoptosis resulting from IL-5 withdrawal
Summary
The alarmin IL-33 is a member of the IL-1 family which is rapidly released during tissue damage and serves as an important mediator of barrier immunity in skin, lung and intestine [1]. Eosinophil-derived IL-4/IL-13 appears to be important for maintenance of alternatively activated macrophages involved in glucose homeostasis in adipose tissues [16]. Another study revealed that eosinophils are recruited to liver lesions where they release IL-4/IL-13 to induce hepatocyte proliferation, an important step in liver regeneration [18]. Given these manifold functions of eosinophils in immunity against helminths, allergy, tissue regeneration and metabolism, specific interventions to modulate survival and IL-4/IL-13 release from eosinophils could be a promising therapeutic approach. We observed that IL-33 acts directly on eosinophils and protects them from spontaneous apoptosis upon growth factor deprivation This effect was dependent on MyD88 signaling and was observed with LPS stimulation. Coculture experiments with purified eosinophils and macrophages revealed that IL-33-induced differentiation of alternatively activated macrophages was dependent on eosinophil-derived IL-4/IL-13 and enhanced in the presence of GM-CSF
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
