The deleterious role of basophils in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus is a complex autoimmune disease of multifactorial origins. All compartments of the immune system appear to be affected, at least in some way, and to contribute to disease pathogenesis. Because of an escape from negative selection autoreactive T and B cells accumulate in SLE patients leading to the production of autoantibodies mainly raised against nuclear components and their subsequent deposition into target organs. We recently showed that basophils, in an IgE and IL-4 dependent manner, contribute to SLE pathogenesis by amplifying autoantibody production. Here, we summarize what we have learned about the deleterious role of basophils in lupus both in a mouse model and in SLE patients. We discuss which possible pathways could be involved in basophil activation and recruitment to secondary lymphoid organs during SLE, and how basophils may amplify autoantibody production.

Figure 1. Deleterious interactions between basophils, B and T cells during SLE

Autoreactive T and B cells trigger autoantibody production and CIC formation during SLE. Activated basophils migrate to lymph nodes where they can interact with both B and T cells. Through secretion of IL-4, IL-6, IL-5, IL-13 and membrane expression of CD40L, BAFF and APRIL, basophils interact with the B cell compartment. They induce autoreactive B cell proliferation, class switch (towards IgG, IgA and IgE), maturation, plasma cell survival and autoantibody production via relevant receptors expressed on B and plasma cells. Basophil-expressed CD40 and MHC class II can activate naïve T cells via CD40L and T cell receptor (TCR) respectively. Activated T Cells secrete IL-3 which induces basophils to secrete IL3 to sustain their own activation and survival. Basophils can drive the Th17 differentiation by secreting IL6 and histamine. Th17 cells promote germinal center formation and support autoantibody production. Through IL-4, Thymic stromal lymphopoietin (TSLP), IL-25 and retinoic acid secretion, together with MHC class II and CD40 surface expression, basophils induce Th2 differentiation of CD4+ T cells. Once primed by basophils, Th2 cells secrete large amounts of IL-4 to support their own generation. This IL-4, together with IL-5, IL-6, IL-10, IL-13 and cell-cell interactions drive autoantibody production by the B cell compartment.