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A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells

Abstract : B cells may have a negative regulatory role, mainly mediated by interleukin 10 (IL-10). We recently showed that regulatory B-cell functions are impaired in patients with rheumatoid arthritis (RA) and that mice transgenic for a proliferation-inducing ligand (APRIL) are protected against collagen-induced arthritis. We aimed to explore the effect of APRIL on human B-cell IL-10 production, in healthy subjects and in patients with RA. The IL-10 production of B-cell was greater with APRIL than with BLyS or control medium, in a dose dependent manner. TACI expression was greater in IL-10 producing B cells (B10) than non-IL-10-producing B cells whereas BAFF-R expression was lower. TNF-α and IFN-γ secretion of T-cells were decreased by APRIL-stimulated B cells. APRIL stimulated STAT3 and STAT3 inhibition decreased B10 cells. APRIL also promoted B10 cells in RA patients. In conclusion, APRIL but not BLyS promotes IL-10 production by CpG-activated B cells and enhances the regulatory role of B cells on T cells. B10 cells in RA patients are responsive to APRIL, which suggests a possible therapeutic application of APRIL to expand B10 cells. This could also explain the difference of clinical efficacy observed between belimumab and atacicept in RA.
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https://hal.archives-ouvertes.fr/hal-01864697
Contributor : Anthony Herrada <>
Submitted on : Thursday, August 30, 2018 - 1:50:52 PM
Last modification on : Friday, May 15, 2020 - 12:22:04 PM

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Charlotte Hua, Rachel Audo, Nataliya Yeremenko, Dominique Baeten, Michael Hahne, et al.. A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells. Journal of Autoimmunity, Elsevier, 2016, 73, pp.64 - 72. ⟨10.1016/j.jaut.2016.06.002⟩. ⟨hal-01864697⟩

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