Full Papers
Leptin accelerates B cell dysfunctions via activating JAK/STAT3/5 and ERK1/2 pathways in patients with systemic lupus erythematosus
H. Chen1, J. Qi2, T. Liu3, M. Zou4, Y. Hu5, J. Wei6, X. Li7, F. Yuan8
- Department of Rheumatology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, and Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
- Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
- Department of Rheumatology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
- Department of Rheumatology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
- Department of Rheumatology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
- Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
- Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, China. lixia416@163.com
- Department of Rheumatology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. yfh222222@163.com
CER15209
2022 Vol.40, N°11
PI 2125, PF 2132
Full Papers
PMID: 35084324 [PubMed]
Received: 02/10/2021
Accepted : 17/12/2021
In Press: 25/01/2022
Published: 05/11/2022
Abstract
OBJECTIVES:
Our previous studies found that serum leptin was increased significantly in SLE, characterised by dysregulated autoreactive B cells producing excessive inflammatory cytokines and autoantibodies. The aim of this study was to explore the effects of leptin on B cell functions in SLE and clarify the key pathways in leptin dysregulated B cells.
METHODS:
Peripheral blood samples were obtained from 86 SLE patients and 28 normal controls. Purified B cells were stimulated with leptin or SLE serum and with or without anti-leptin antibody. The frequencies of CD19-CD138+ plasma cells and the expression of leptin receptor (LEPR) on B cells were determined with flow cytometry. The levels of antibodies and cytokines were assayed by ELISA. Classic signalling pathways were detected with western blotting method.
RESULTS:
Increased plasma cells and the levels of IgG and anti-dsDNA antibodies were positively correlated with serum leptin in SLE patients. LEPR+CD19+B cells were increased in SLE patients. Leptin up-regulated LEPR on B cells and activated B cells to produce higher levels of IL-6, IL-10 and TNF-α, and induced B cells to differentiated into plasma cells secreting more IgG and IgM. More importantly, anti-leptin neutralising antibody could partially restore increased cytokines, antibodies and plasma cells induced by SLE serum. Mechanistically, both leptin and SLE serum activated JAK/STAT3/5 and ERK1/2 signalling pathways in B cells, and the secretion-enhancing effects were restored by their inhibitors.
CONCLUSIONS:
Leptin may be a key factor leading to B cell dysfunction by activating JAK/STAT3/5 and ERK1/2 signalling pathways in SLE.
