한빛사 논문
Abstract
Je-Min Choia,b,c, Jae-Hun Shind,e, Myung-Hyun Sohnf, Martha J. Hardingg, Jong-Hyun Parkd, Zuzana Tobiasovac, Da-Young Kimd, Stephen E. Maherc, Wook-Jin Chaec, Sung-Ho Parkd, Chun-Geun Leeh, Sang-Kyou Leed,1, and Alfred L. M. Bothwellc,1
aDepartment of Life Science, Hanyang University, Seoul 133-791, Republic of Korea;
bHanyang Biomedical Research Institute, Seoul 133-791, Republic of Korea;
cDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;
dDepartment of Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Republic of Korea;
eSpecific Organs Cancer Branch, Research Institute National Cancer Center, Goyang, Gyeonnggi 410-769, Republic of Korea;
fDepartment of Pediatrics and Institute of Allergy, Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 102-752, Republic of Korea;
gSection of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06519; and
hSection of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520
Edited* by Sherman M. Weissman, Yale University, New Haven, CT, and approved September 14, 2010 (received for review January 12, 2010)
Abstract
Foxp3 is a key transcription factor for differentiation and function of regulatory T (Treg) cells that is critical for maintaining immunological self-tolerance. Therefore, increasing Treg function by Foxp3 transduction to regulate an inflammatory immune response is an important goal for the treatment of autoimmune and allergic diseases. Here we have generated a cell-permeable Foxp3 protein by fusion with the unique human HHph-1-PTD (protein transduction domain), examined its regulatory function in T cells, and characterized its therapeutic effect in autoimmune and allergic disease models. HHph-1-Foxp3 was rapidly and effectively transduced into cells within 30 min and conferred suppressor function to CD4+CD25- T cells as well as directly inhibiting T-cell activation and proliferation. Systemic delivery of HHph-1 Foxp3 remarkably inhibited the autoimmune symptoms of scurfy mice and the development of colitis induced by scurfy or wild-type CD4 T cells. Moreover, intranasal delivery of HHph-1-Foxp3 strongly suppressed ovalbumin-induced allergic airway inflammation. These results demonstrate the clinical potential of the cell-permeable recombinant HHph-1-Foxp3 protein in autoimmune and hypersensitive allergic diseases.
protein transduction domain, immunotherapy, autoimmunity, allergy
Footnotes
1To whom correspondence may be addressed.
Author contributions: J.-M.C., A.L.M.B., and S.-K.L. designed research; J.-M.C., J.-H.S., and J.-H.P. performed research; M.-H.S., M.J.H., Z.T., D.-Y.K., S.E.M., W.-J.C., S.-H.P., and C.-G.L. contributed new reagents/analytic tools; J.-M.C., C.-G.L., S.-K.L., and A.L.M.B. analyzed data; and J.-M.C., S.-K.L., and A.L.M.B. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1000400107/-/DCSupplemental.
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