Abstract
Foxp3 is the master transcription factor for T regulatory (Treg) cell differentiation and function. This study aimed to test the therapeutic potential of cell penetrating recombinant Foxp3 protein in arthritis. Recombinant Foxp3 protein was fused to a cell penetrating polyarginine (Foxp3-11R) tag to facilitate intracellular transduction. In vitro Foxp3-11R treated CD4(+) T cells showed a 50% increase in suppressive function compared with control protein treated cells. Severity of arthritis in Foxp3-11R treated mice was significantly reduced compared with those treated with a control protein. CD4(+) T cells of lymph nodes and spleen from Foxp3-11R treated mice showed increased levels of Foxp3 expression compared with those of a control protein treated. These results demonstrated that Foxp3-11R can enhance T cell suppressive function and ameliorate experimental arthritis and suggest that cell penetrating recombinant Foxp3 is a potentially useful agent in therapy of arthritis.
Published by Elsevier Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Arthritis, Experimental / chemically induced
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Arthritis, Experimental / metabolism
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Arthritis, Experimental / therapy*
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Cell Membrane / metabolism
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Cell Membrane Permeability
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Cell Proliferation
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Culture Media / metabolism
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Female
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Forkhead Transcription Factors / administration & dosage
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism*
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Forkhead Transcription Factors / therapeutic use
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Humans
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Interleukin-2 Receptor alpha Subunit / metabolism
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Mice
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Peptides / metabolism
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Protein Transport
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / therapeutic use
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Spleen / metabolism
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Spleen / pathology
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T-Lymphocytes, Regulatory / metabolism*
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Zymosan / adverse effects
Substances
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Culture Media
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FOXP3 protein, human
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Forkhead Transcription Factors
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Il2ra protein, mouse
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Interleukin-2 Receptor alpha Subunit
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Peptides
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Recombinant Fusion Proteins
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polyarginine
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Zymosan