Basophil Activation-Dependent Autoantibody and Interleukin-17 Production Exacerbate Systemic Lupus Erythematosus

Abstract

ObjectiveAutoantibody and inflammatory cytokines play crucial roles in the development of systemic lupus erythematosus (SLE); however, the regulation of their production warrants further investigation. This study aimed to investigate the role of basophil activation in the development of SLE based on studies in patients with SLE and spontaneous lupus-prone MRL-lpr/lpr mice.MethodsThe phenotypes of peripheral basophils and the production of autoantibody and interleukin (IL)-17 in patients with SLE were determined by flow cytometry and enzyme-linked immunosorbent assay, and also their correlations were investigated by statistical analysis. Thereafter, the effect of basophils on autoantibody production by B cells and Th17 differentiation in SLE were evaluated in vitro. Finally, the effect of basophil depletion on the development of autoimmune disorders in spontaneous lupus-prone MRL-lpr/lpr mice was examined.ResultsThe decreased numbers and an increased activation of peripheral basophils were found to be correlated with increased autoantibody production and disease activity in patients with SLE. Correspondingly, in vitro coculture studies showed that basophils obtained from patients with SLE promoted autoantibody production by SLE B cells and promoted Th17 differentiation from SLE naïve CD4+ T cells. The decrease of peripheral basophils in patients with SLE might be due to their migration to lymph nodes post their activation mediated by (autoreactive) IgE as supported by their increased CD62L and CCR7 expressions and accumulation in the lymph nodes of MRL-lpr/lpr mice. Furthermore, an increased activation of peripheral basophils was identified in MRL-lpr/lpr mice. Importantly, basophil-depleted MRL-lpr/lpr mice exhibited an extended life span, improved renal function, and lower serum levels of autoantibodies and IL-17, while basophil-adoptive-transferred mice exhibited the opposite results.ConclusionThese finding suggest that basophil activation-dependent autoantibody and IL-17 production may constitute a critical pathogenic mechanism in SLE.

Human mast cells and basophils—How are they similar how are they different?

“…Lower numbers of peripheral blood basophils but increased activation markers were found in patients with SLE. Interestingly, basophil depletion in animals genetically predisposed to develop SLE reduced disease severity . A recent study confirmed the relevance of basophil in a genetically independent model of SLE .…”

“…This finding suggests that mast cells could play important and probably multifaceted roles in patients with RA, which need additional investigations. In SLE mast cells were found to be dispensable whereas basophils may contribute to the pathogenesis of experimental and human SLE …”

Basophil Recruitment to Skin Lesions of Patients with Systemic Lupus Erythematosus Mediated by CCR1 and CCR2

“…They also function as antigen-presenting cells [24-26]. However, their function in autoimmunity remains poorly understood [18, 27]. The role of basophils in mice has been investigated extensively, both in vivo and in vitro [28-31], but not in humans.…”

“…Consistent with this observation, we detected high expression of RANTES and MCP-1 in tissue from skin lesions of SLE patients. Another aspect, migration to lymph nodes mediated by CD62L also contributing to the decrease of peripheral basophils in patients with SLE [18]. …”

“…Cutaneous manifestations are correlated with disease activity in SLE, which gives them diagnostic value [14]. As was known, several types of immune cells [15-17], including basophils [18] have been reported to exacerbate SLE by amplifying production of autoantibodies and inflammatory cytokines. However, we do not know if basophils infiltrate skin lesions in SLE, and if they do, what are the mechanisms of this infiltration.…”