Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice
Alopecia areata (AA) is an autoimmune disease mediated by NKG2D-expressing cytotoxic T lymphocytes destroying hair follicles in the skin. It is one of the most common autoimmune diseases, but there is no effective treatment modality approved by the FDA. Regulatory T cells (Tregs) are crucial for sup...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.874778/full |
| _version_ | 1811241639886192640 |
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| author | Eunjin Lee Eunjin Lee Mingyu Kim You Jeong Lee You Jeong Lee |
| author_facet | Eunjin Lee Eunjin Lee Mingyu Kim You Jeong Lee You Jeong Lee |
| author_sort | Eunjin Lee |
| collection | DOAJ |
| description | Alopecia areata (AA) is an autoimmune disease mediated by NKG2D-expressing cytotoxic T lymphocytes destroying hair follicles in the skin. It is one of the most common autoimmune diseases, but there is no effective treatment modality approved by the FDA. Regulatory T cells (Tregs) are crucial for suppressing autoreactive T cells, and in the skin, they promote hair growth by inducing anagen. Based on this, we tested the therapeutic potential of expanded Tregs in AA using the C3H/HeJ mouse model. In mice with AA, NKG2D-expressing CD8 T cells widely infiltrate both haired and hairless skin areas, which have tissue-resident memory T-cell phenotypes. Tregs in the skin express CD25, CTLA-4, GATA-3, and Jagged1 and efficiently proliferate with IL-2 cytokine antibody complex. However, expanding Tregs in the skin did not induce anagen in normal mice, indicating that they are necessary but not sufficient for anagen induction. Also, they fail to suppress autoreactive CD8 T cells in the skin to reverse established AA in C3H/HeJ mice. These results suggest that Treg expansion alone is not sufficient for AA treatment, and combined immunotherapy is required. |
| first_indexed | 2024-04-12T13:39:00Z |
| format | Article |
| id | doaj.art-72c4d2e8d8dc48da8bf725dd53a15723 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:39:00Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-72c4d2e8d8dc48da8bf725dd53a157232022-12-22T03:30:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.874778874778Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ MiceEunjin Lee0Eunjin Lee1Mingyu Kim2You Jeong Lee3You Jeong Lee4Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South KoreaDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South KoreaDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South KoreaResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South KoreaAlopecia areata (AA) is an autoimmune disease mediated by NKG2D-expressing cytotoxic T lymphocytes destroying hair follicles in the skin. It is one of the most common autoimmune diseases, but there is no effective treatment modality approved by the FDA. Regulatory T cells (Tregs) are crucial for suppressing autoreactive T cells, and in the skin, they promote hair growth by inducing anagen. Based on this, we tested the therapeutic potential of expanded Tregs in AA using the C3H/HeJ mouse model. In mice with AA, NKG2D-expressing CD8 T cells widely infiltrate both haired and hairless skin areas, which have tissue-resident memory T-cell phenotypes. Tregs in the skin express CD25, CTLA-4, GATA-3, and Jagged1 and efficiently proliferate with IL-2 cytokine antibody complex. However, expanding Tregs in the skin did not induce anagen in normal mice, indicating that they are necessary but not sufficient for anagen induction. Also, they fail to suppress autoreactive CD8 T cells in the skin to reverse established AA in C3H/HeJ mice. These results suggest that Treg expansion alone is not sufficient for AA treatment, and combined immunotherapy is required.https://www.frontiersin.org/articles/10.3389/fimmu.2022.874778/fullalopecia areata (AA)TregIL-2anagenhair |
| spellingShingle | Eunjin Lee Eunjin Lee Mingyu Kim You Jeong Lee You Jeong Lee Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice Frontiers in Immunology alopecia areata (AA) Treg IL-2 anagen hair |
| title | Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice |
| title_full | Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice |
| title_fullStr | Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice |
| title_full_unstemmed | Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice |
| title_short | Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice |
| title_sort | selective expansion of tregs using the il 2 cytokine antibody complex does not reverse established alopecia areata in c3h hej mice |
| topic | alopecia areata (AA) Treg IL-2 anagen hair |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.874778/full |
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