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2017 ; 8
(ä): 348
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Basophil Activation-Dependent Autoantibody and Interleukin-17 Production
Exacerbate Systemic Lupus Erythematosus
#MMPMID28396669
Pan Q
; Gong L
; Xiao H
; Feng Y
; Li L
; Deng Z
; Ye L
; Zheng J
; Dickerson CA
; Ye L
; An N
; Yang C
; Liu HF
Front Immunol
2017[]; 8
(ä): 348
PMID28396669
show ga
OBJECTIVE: Autoantibody 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. METHODS: The
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. RESULTS: The
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. CONCLUSION:
These finding suggest that basophil activation-dependent autoantibody and IL-17
production may constitute a critical pathogenic mechanism in SLE.
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