Basophils and IgE: Linking the Allergic Environment to Autoimmunity

As outlined in some of the accompanying articles in this issue, the role of the basophil as an effector cell in al- lergy and in host defense (particularly to parasites) has long been recognized. However, recent advances advocate for the basophil as an immunomodulatory cell that can promote naive CD4 + T cell commitment to Th2 cell differentiation. While this is in keeping with the concept that the basophil is important in an allergic environment, new discoveries suggest that basophils may be immunomodulatory beyond the context of allergic disease. Here we mainly discuss our own work, which provides a new paradigm for the role of basophils beyond allergy. Our findings demonstrate the importance of autoreactive IgE's, IL-4 and basophils in promoting autoantibody production and the development of lupus nephritis. The conclusions drawn are based on studies in a mouse model (Lyn -/- mice) of spontaneous systemic lupus erythematosus (SLE)-like disease as well as from analysis of the relationship between disease activity in SLE patients and their levels of autoreactive IgE's and activated basophils with antigen presenting capability. The findings demonstrate a link between the Th2 environment and autoimmunity and provide new areas of investigation with therapeutic potential.