Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

Je Min Choi, Jae Hun Shin, Myung Hyun Sohn, Martha J. Harding, Jong Hyun Park, Zuzana Tobiasova, Da Young Kim, Stephen E. Maher, Wook Jin Chae, Sung Ho Park, Chun Geun Lee, Sang Kyou Lee, Alfred L.M. Bothwell

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 aswell 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.

Original languageEnglish
Pages (from-to)18575-18580
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number43
DOIs
Publication statusPublished - 2010 Oct 26

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Inflammatory Bowel Diseases
Autoimmune Diseases
Inflammation
T-Lymphocytes
Regulatory T-Lymphocytes
Proteins
Self Tolerance
Ovalbumin
Therapeutic Uses
Colitis
Transcription Factors
Cell Proliferation
Therapeutics

All Science Journal Classification (ASJC) codes

  • General

Cite this

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. / Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 43. pp. 18575-18580.
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Choi, JM, Shin, JH, Sohn, MH, Harding, MJ, Park, JH, Tobiasova, Z, Kim, DY, Maher, SE, Chae, WJ, Park, SH, Lee, CG, Lee, SK & Bothwell, ALM 2010, 'Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 43, pp. 18575-18580. https://doi.org/10.1073/pnas.1000400107

Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. / 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 43, 26.10.2010, p. 18575-18580.

Research output: Contribution to journalArticle

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T1 - Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

AU - Choi, Je Min

AU - Shin, Jae Hun

AU - Sohn, Myung Hyun

AU - Harding, Martha J.

AU - Park, Jong Hyun

AU - Tobiasova, Zuzana

AU - Kim, Da Young

AU - Maher, Stephen E.

AU - Chae, Wook Jin

AU - Park, Sung Ho

AU - Lee, Chun Geun

AU - Lee, Sang Kyou

AU - Bothwell, Alfred L.M.

PY - 2010/10/26

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N2 - 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 aswell 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.

AB - 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 aswell 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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