title: Cell penetrating recombinant Foxp3 protein enhances Treg function and ameliorates arthritis.
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.
authors.affiliation: Oregon Health & Science University and Portland VA Medical Center, 3181 S.W. Sam Jackson Park Rd, OP09, Portland, OR 97239-3098, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yomogida
authors.forename: Shili
authors.initials: S
authors.lastname: Wu
authors.forename: Bobby
authors.initials: B
authors.lastname: Baravati
authors.forename: Camilo
authors.initials: C
authors.lastname: Avendano
authors.forename: Tom
authors.initials: T
authors.lastname: Caldwell
authors.forename: Brian
authors.initials: B
authors.lastname: Maniaci
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Cong-Qiu
authors.initials: CQ
authors.lastname: Chu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D049109:Cell Proliferation; D003470:Culture Media / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D015054:Zymosan / Q000009:adverse effects
chemical_list: D003470:Culture Media; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D010455:Peptides; D011993:Recombinant Fusion Proteins; C015462:polyarginine; D015054:Zymosan
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