Interleukin (IL)-39 [IL-23p19/Epstein–Barr virus-induced 3 (Ebi3)] induces differentiation/expansion of neutrophils in lupus-prone mice

• DOI: 10.1111/cei.12840
• Publication Date: 2016-07-12T00:06:52Z
• Authors: X Wang; X Liu; Y Zhang; Z Wang; G Zhu; G Han; G Chen; C Hou; T Wang; N Ma; B Shen; Y Li; H Xiao; R Wang
• Keywords: Mice, Knockout; STAT3 Transcription Factor; Mice, Inbred MRL lpr; 0303 health sciences; CD11b Antigen; Neutrophils; B-Lymphocyte Subsets; Gene Expression; Cell Differentiation; Antigens, Differentiation; Cell Line; 3. Good health; Minor Histocompatibility Antigens; Mice; 03 medical and health sciences; B-Cell Activating Factor; Interleukin-23 Subunit p19; Animals; Female; Receptors, Cytokine; Biomarkers; Cells, Cultured

Summary Interleukin (IL)-12 family cytokines play critical roles in autoimmune diseases. Our previous study has shown that IL-23p19 and Epstein–Barr virus-induced 3 (Ebi3) form a new IL-12 family heterodimer, IL-23p19/Ebi3, termed IL-39, and knock-down of p19 or Ebi3 reduced diseases by transferred GL7+ B cells in lupus-prone mice. In the present study, we explore further the possible effect of IL-39 on murine lupus. We found that IL-39 in vitro and in vivo induces differentiation and/or expansion of neutrophils. GL7+ B cells up-regulated neutrophils by secreting IL-39, whereas IL-39-deficient GL7+ B cells lost the capacity to up-regulate neutrophils in lupus-prone mice and homozygous CD19cre (CD19-deficient) mice. Finally, we found that IL-39-induced neutrophils had a positive feedback on IL-39 expression in activated B cells by secreting B cell activation factor (BAFF). Taken together, our results suggest that IL-39 induces differentiation and/or expansion of neutrophils in lupus-prone mice.