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Therapeutic Effects of anti-Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Treatment in Psoriasis and Arthritis

Therapeutic Effects of anti-Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Treatment in Psoriasis and Arthritis

Pilar Alvarez, Juan Jesús Augustín, Esther Tamayo, Marcos Iglesias, Olga Acinas, M Angeles Mendiguren, José Andrés Vázquez, Fernanda Genre, David San Segundo, Jesús Merino, Ramón Merino

Arthritis Rheumatol. 2020 Apr 6.

PMID: 32249544

Abstract:

Objectives:
Transforming growth factor beta (TGFβ) inhibitor Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor (BAMBI) has been shown to control CD4+ T lymphocytes differentiation into either tolerogenic regulatory T (Tregs) or pathogenic TH 17 cells through the regulation of TGFβ and IL-2 signaling strength. In the present study, we explore the potential beneficial effects of its pharmacological inhibition with new anti-BAMBI monoclonal antibodies (mAbs) in different skin and joint experimental chronic-inflammatory/autoimmune diseases.
Methods:
Development of saccharomyces cerevisiae mannan-induced psoriatic arthritis (MIP) (n= 18-30 mice/group), imiquimod-induced skin psoriasis (n= 20-30 mice/group) or collagen type II-induced arthritis (CIA) (n= 13-16 mice/group) was analyzed in a total number of 2-5 different experiments with B10.RIII wild type (WT) or BAMBI-deficient mice treated or not with B101.37 (mouse IgG1 anti-BAMBI), mouse IgG1 anti-TNP isotype control, anti-CD25 or anti-TGFβ mAbs.
Results:
Treatment of normal mice with an IgG1 anti-BAMBI mAb, clone B101.37, expands Tregs in vivo and has both preventive and therapeutic effects in the murine model of MIP (p<0.05 in both cases). Disease protection is mediated by Tregs, which control the activation and expansion of pathogenic IL-17-producing cells, and is dependent on TGFβ. Furthermore, B101.37 treatment blocks the development of skin psoriasis induced by imiquimod and of CIA (p<0.05 in both cases). Finally, the pharmacological inhibition of BAMBI with the IgM anti-BAMBI B143.14 mAb also potentiates the suppressive activity of Tregs in vitro (p<0.001).
Conclusions:
We identify BAMBI as a promising new therapeutic target for chronic-inflammatory diseases and other pathological conditions modulated by Tregs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248728	Monoclonal Anti-Bone Morphogenetic Protein 2 antibody produced in mouse			Price

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