A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells. (September 2016)

• Record Type: Journal Article
• Authors: Hua, Charlotte; Audo, Rachel; Yeremenko, Nataliya; Baeten, Dominique; Hahne, Michael; Combe, Bernard; Morel, Jacques; Daïen, Claire
• Is Part Of: Journal of autoimmunity. Volume 73(2016)
• Page Start: 64
• Page End: 72
• Publication Date: 2016-09
• Subjects: APRIL -- B-lymphocytes -- Interleukin-10 -- Rheumatoid arthritis; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2016.06.002
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: APRIL promotes IL-10 production of B-cells in healthy subjects and RA patients. BLyS does not promote IL-10 production of B-cells in healthy subjects and RA patients. IL-10 producing B cells express more TACI and less BAFF-R than IL-10–non-producing B cells. APRIL may be useful to restore IL-10 production of B-cells in RA patients. APRIL may be useful to restore B-cell regulatory functions in RA patients.