1. Academic Validation
  2. The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhi Regulatory B-Cell Subset in Lupus

The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhi Regulatory B-Cell Subset in Lupus

  • J Invest Dermatol. 2017 Dec;137(12):2532-2543. doi: 10.1016/j.jid.2017.07.843.
Yamin Zhang 1 Jun Li 2 Nuoya Zhou 1 Yi Zhang 1 Min Wu 3 Jian Xu 4 Chen Shen 1 Xiangjie An 1 Guanxin Shen 3 Ming Yang 5 Chun Zhang 6 Juan Tao 7
Affiliations

Affiliations

  • 1 Department of Dermatology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China.
  • 2 Department of Dermatology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China; Department of Dermatology, The Central Hospital of Wuhan, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China.
  • 3 Department of Immunology, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China.
  • 4 Department of Hematology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China.
  • 5 Department of Dermatology, The Central Hospital of Wuhan, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China.
  • 6 Department of Nephrology, Union Hospital, Tongji Medical College, HUST, Wuhan, Hubei, China.
  • 7 Department of Dermatology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: tjhappy@126.com.
Abstract

IL-35 is a critical immunosuppressive cytokine that plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in systemic lupus erythematosus, also a dichotomous regulator for B-cell immune responses, has an effect on IL-35-producing regulatory B cells and their underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Faslpr/lpr mice. BAFF-induced IL-35-producing B cells were mainly from the marginal zone B-cell subset and exhibited a CD5+CD1dhiFcγRIIbhi phenotype. These IL-35-producing regulatory B-cell subsets exhibited regulatory effects on both CD4+CD25- T cells and CD4+CD25+ regulatory T cells. We further identified that BAFF-TACI interaction could induce the production of IL-35 through the classical NF-κB1 pathway. In vivo study also showed that BAFF could facilitate IL-35 secretion in marginal zone B cells, whereas anti-BAFF treatment could decrease the frequency of IL-35-producing CD5+CD1dhiFcγRIIbhi B cells in MRL-Faslpr/lpr mice. We showed that BAFF could induce IL-35 production by a unique CD5+CD1dhiFcγRIIbhi regulatory B-cell subset mainly through TACI activation in lupus, providing an advanced understanding of the regulatory effect of BAFF in autoimmune diseases.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15473
    99.76%, IKKβ 抑制剂
    IKK