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Title

BAMBI, a new molecular target in autoimmunity

AuthorsÁlvarez, Pilar; Augustin, Juan Jesús; Tamayo, Esther; Iglesias, Marcos ; Merino, Jesús; Merino, Ramón
Issue Date12-May-2017
CitationIMMUNOLOGY 2017
AbstractWe have previous demonstrated that BAMBI (BMP and Activin Membrane Bound Inhibitor) negatively regulates the functional differentiation of CD4 T cells into tolerogenic regulatory T-cells (Tregs) and positively the differentiation into pro-inflammatory TH17 cells. Accordingly, mice deficient in BAMBI are resistant against the development of collagen type II-induced arthritis (CIA). To analyze the therapeutic effects of BAMBI inhibition in normal mice in the development of autoimmunity, we developed new inhibitory mouse anti-mouse BAMBI mAbs. Treatment of B10RIII wild type (WT) mice with a high dose of a mouse IgG1 anti-mouse BAMBI mAb (clone B101.37; 2 mg/mice/week), but not with a low dose of B101.37 (0.3 mg/mice/week) or a high dose of an irrelevant IgG1 mAb (2 mg/mice/week), inhibited the development of CIA as efficiently as observed in B10RIII.BAMBI-KO mice. We further explore the therapeutic potential of B101.37 in experimental models of psoriasis (Ps) and psoriasis arthritis (PsA). A single ip injection of mannan from Saccharomyces cerevisiae induces an acute inflammation resembling human Ps and PsA in B10RIII.WT but with a reduced severity in B10RIII.BAMBI-KO mice. Again, treatment of WT mice with B101.37, but not with an irrelevant IgG1 antibody, protects the animals against mannan-induced PsA and Ps by a Treg- and TGFß-dependent mechanism. B101.37 also exhibits a therapeutic activity against mannan-induced PsA and Ps once the disease has been established. Similar results have been observed in a model of Ps induced after the topic administration of the TLR-7 agonist imiquimod. Altogether, our results demonstrate the beneficial effects of BAMBI inhibitors in the treatment of autoimmune skin and joint diseases.
DescriptionResumen del póster presentado al Annual Meeting of the American-Association-of-Immunologists, celebrado en Washington (US) del 12 al 16 de mayo de 2017.
URIhttp://hdl.handle.net/10261/164844
Appears in Collections:(IBBTEC) Comunicaciones congresos
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