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

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 CD19(cre) (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.