Therapeutic Effects of Anti-Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Treatment in Psoriasis and Arthritis.
Adjuvants, Immunologic
/ toxicity
Animals
Antibodies, Monoclonal
/ pharmacology
Arthritis, Experimental
/ immunology
Arthritis, Psoriatic
/ chemically induced
CD4-Positive T-Lymphocytes
/ drug effects
Cell Differentiation
/ drug effects
Collagen Type II
Disease Models, Animal
Imiquimod
/ toxicity
Interleukin-17
/ immunology
Interleukin-2
/ immunology
Mannans
Membrane Proteins
/ antagonists & inhibitors
Mice
Mice, Knockout
Psoriasis
/ immunology
Saccharomyces cerevisiae
Skin
/ drug effects
T-Lymphocytes, Regulatory
/ drug effects
Th17 Cells
/ drug effects
Transforming Growth Factor beta
/ drug effects
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
25
03
2019
accepted:
24
03
2020
pubmed:
7
4
2020
medline:
12
1
2021
entrez:
7
4
2020
Statut:
ppublish
Résumé
The transforming growth factor β (TGFβ) inhibitor BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) has been shown to control differentiation of CD4+ T lymphocytes into either tolerogenic Treg cells or pathogenic Th17 cells, through the regulation of TGFβ and interleukin-2 (IL-2) signaling strength. The present study was undertaken to explore the potential beneficial effects of this strategy of pharmacologic inhibition using novel anti-BAMBI monoclonal antibodies (mAb) in different experimental murine models of chronic skin and joint inflammatory/autoimmune disease. Development of Saccharomyces cerevisiae mannan-induced psoriatic arthritis (MIP) (n = 18-30 mice per group), imiquimod-induced skin psoriasis (n = 20-30 mice per group), or type II collagen-induced arthritis (CIA) (n = 13-16 mice per group) was analyzed in a total of 2-5 different experiments with either wild-type (WT) or BAMBI-deficient B10.RIII mice that were left untreated or treated with mAb B101.37 (mouse IgG1 anti-BAMBI), a mouse IgG1 anti-TNP isotype control, anti-CD25, or anti-TGFβ mAb. Treatment of normal mice with IgG1 anti-BAMBI mAb clone B101.37 led to expansion of Treg cells in vivo, and had both preventive and therapeutic effects in mice with MIP (each P < 0.05 versus controls). The conferred protection against disease progression was found to be mediated by Treg cells, which controlled the activation and expansion of pathogenic IL-17-producing cells, and was dependent on the level of TGFβ activity. Furthermore, treatment with B101.37 mAb blocked both the development of skin psoriasis induced by imiquimod and the development of CIA in mice (each P < 0.05 versus controls). Finally, pharmacologic inhibition of BAMBI with the IgM anti-BAMBI mAb B143.14 also potentiated the suppressive activity of Treg cells in vitro (P < 0.001 versus controls). These results in murine models identify BAMBI as a promising new therapeutic target for chronic inflammatory diseases and other pathologic conditions modulated by Treg cells.
Substances chimiques
Adjuvants, Immunologic
0
Antibodies, Monoclonal
0
Bambi protein, mouse
0
Collagen Type II
0
Il17a protein, mouse
0
Interleukin-17
0
Interleukin-2
0
Mannans
0
Membrane Proteins
0
Transforming Growth Factor beta
0
Imiquimod
P1QW714R7M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1547-1558Informations de copyright
© 2020, American College of Rheumatology.
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