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2016 ; 8
(331
): 331ra40
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Arginase-1-dependent promotion of TH17 differentiation and disease progression by
MDSCs in systemic lupus erythematosus
#MMPMID27009269
Wu H
; Zhen Y
; Ma Z
; Li H
; Yu J
; Xu ZG
; Wang XY
; Yi H
; Yang YG
Sci Transl Med
2016[Mar]; 8
(331
): 331ra40
PMID27009269
show ga
Expansion of myeloid-derived suppressor cells (MDSCs) has been documented in some
murine models and patients with autoimmune diseases, but the exact role of MDSCs
in this process remains largely unknown. The current study investigates this
question in patients with systemic lupus erythematosus (SLE). Patients with
active SLE showed a significant increase in HLA-DR(-)CD11b(+)CD33(+)MDSCs,
including both CD14(+)CD66b(-)monocytic and CD14(-)CD66b(+)granulocytic MDSCs, in
the peripheral blood compared to healthy controls (HCs). The frequency of MDSCs
was positively correlated with the levels of serum arginase-1 (Arg-1) activity, T
helper 17 (TH17) responses, and disease severity in SLE patients. Consistently,
in comparison with MDSCs from HCs, MDSCs from SLE patients exhibited
significantly elevated Arg-1 production and increased potential to promote TH17
differentiation in vitro in an Arg-1-dependent manner. Moreover, in a humanized
SLE model, MDSCs were essential for the induction of TH17 responses and the
associated renal injuries, and the effect of MDSCs was Arg-1-dependent. Our data
provide direct evidence demonstrating a pathogenic role for MDSCs in human SLE.
This study also provides a molecular mechanism of the pathogenesis of SLE by
demonstrating an Arg-1-dependent effect of MDSCs in the development of TH17
cell-associated autoimmunity, and suggests that targeting MDSCs or Arg-1 may
offer potential therapeutic strategies for the treatment of SLE and other TH17
cell-mediated autoimmune diseases.