B10 Cells Ameliorate the Progression of Lupus Nephritis by Attenuating Glomerular Endothelial Cell Injury.
OBJECTIVE
B10 cells are generally considered to inhibit the kidney injury in systemic lupus erythematosus (SLE) mouse models, but recently this function of B10 cells was denied by the lineage-specific deletion of IL-10 from B cells. Thus, this study aimed to determine whether and how B10 cells play a protective role in lupus nephritis (LN).


METHODS
LN and non-LN SLE patients without receiving any treatments were recruited, and the percentages of circulating B10 cell were determined. Furthermore, the purified B10 cells were transferred into MRL/lpr SLE mice, and the exact effects of B10 cells on LN progression were investigated.


RESULTS
The percentage of circulating B10 cells was significantly higher in patient than in healthy controls, while they were fewer in LN patients than non-LN SLE patients. Moreover, B10 cells rather than plasma IL-10 levels were negatively correlated with disease severity especially with kidney injury in LN patients. In animal experiments, the glomerular injuries including the proteinuria and pathological scores were significantly attenuated in SLE mice transferred with B10 cells, accompanied by the decreased glomerular endothelial cell CD54/CD106 expression, and glomerular p38 phosphorylation as well as increased SOCS3 expression. At the same time, the serum anti-dsDNA autoantibody, TNF-α and IFN-γ levels were also reduced, while there were no changes in serum IL-10 and IL-17 levels in B10 cell transferred mice.


CONCLUSIONS
These findings suggest that B10 cells could - independent from IL-10 - ameliorate glomerular injury in LN through protection of glomerular endothelial cells.
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Miao
M
Yu
You
Y
Song
Ming-Xin
MX
Zhu
Wei
W
Liang
Qi
Q
Long
Pei-Wu
PW
Ding
Yu
Y
Xie
Yu-Hua
YH
Liao
Jing
J
Yuan
D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000473:pathology*; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D008297:Male; D019463:Mice, Inbred MRL lpr; D012720:Severity of Illness Index
D016753:Interleukin-10