Effects of BAMBI deficiency in the development of Systemic Lupus Erythematosus

Abstract

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies and immune complexes deposition in various organs. Follicular CD4+ T cells play a crucial role in this autoimmune syndrome by activating autoreactive germinal center B cells. The transforming growth factor β (TGBβ) inhibitor BAMBI (Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor) is known to control the differentiation of CD4+ T lymphocytes into either tolerogenic Tregs or pathogenic Th17 cells. BAMBI absence in mutant mice or its pharmacological inhibition with the B101.37 monoclonal antibody promotes an increase in Treg differentiation and activity and at the same time, a reduction in Th17 cell differentiation, resulting in the inhibition of autoimmune disease development. Based on these findings, in the present study we have analysed the effects of BAMBI deficiency in the development of SLE. We have employed the chronic graft-versus-host disease lupus model induced after the transference of 40–60 × 106 lymphocytes from B6 or B6-BAMBI-KO mice into either Bm12 or Bm12-BAMBI-KO recipients. As reported previously, Bm12 mice receiving lymphocytes from B6 mice produce high levels of circulating IgG anti-DNA and anti-nucleosomal autoantibodies and exhibit linear glomerular IgG deposits in their kidneys. In contrast, both Bm12 mice injected with allogeneic B6-BAMBI-KO lymphocytes and Bm12-BAMBI-KO recipients receiving lymphocytes from B6 donors do not produce significant levels of circulating autoantibodies and do not reveal immune complexes deposits. Taken together, these results indicate that the absence of BAMBI in either donor or recipient lymphocytes protects mice against the development of SLE.