Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammationopen access
- Authors
- Choi, Je-Min; Shin, Jae-Hun; Sohn, Myung-Hyun; Harding, Martha J.; Park, Jong-Hyun; Tobiasova, Zuzana; Kim, Da-Young; Maher, Stephen E.; Chae, Wook-Jin; Park, Sung-Ho; Lee, Chun-Geun; Lee, Sang-Kyou; Bothwell, Alfred L. M.
- Issue Date
- Oct-2010
- Publisher
- NATL ACAD SCIENCES
- Keywords
- protein transduction domain; immunotherapy; autoimmunity; allergy
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.43, pp.18575 - 18580
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 107
- Number
- 43
- Start Page
- 18575
- End Page
- 18580
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/173674
- DOI
- 10.1073/pnas.1000400107
- ISSN
- 0027-8424
- 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.
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