Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis
Summary: T regulatory cells (Tregs) are a potential therapeutic target in many autoimmune diseases including rheumatoid arthritis (RA). The mechanisms responsible for the maintenance of Tregs in chronic inflammatory conditions such as RA are poorly understood. We employed our mouse model of RA in wh...
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Elsevier
2023-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223008118 |
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| author | Qi-Quan Huang Yiwei Hang Renee Doyle Qinwen Mao Deyu Fang Richard M. Pope |
| author_facet | Qi-Quan Huang Yiwei Hang Renee Doyle Qinwen Mao Deyu Fang Richard M. Pope |
| author_sort | Qi-Quan Huang |
| collection | DOAJ |
| description | Summary: T regulatory cells (Tregs) are a potential therapeutic target in many autoimmune diseases including rheumatoid arthritis (RA). The mechanisms responsible for the maintenance of Tregs in chronic inflammatory conditions such as RA are poorly understood. We employed our mouse model of RA in which, the following deletion of Flice-like inhibitory protein in CD11c+ cells, CD11c-FLIP-KO (HUPO) mice develop spontaneous, progressive, erosive arthritis, with reduced Tregs, and the adoptive transfer of Tregs ameliorates the arthritis. HUPO thymic Treg development was normal, but peripheral of Treg Foxp3 was diminished mediated by reduction of dendritic cells and interleukin-2 (IL-2). During chronic inflammatory arthritis Tregs fail to maintain Foxp3, leading to non-apoptotic cell death and conversion to CD4+CD25+Foxp3- cells. Treatment with IL-2 increased Tregs and ameliorated the arthritis. In summary, reduced dendritic cells and IL-2 in the milieu of chronic inflammation, contribute to Treg instability, promoting HUPO arthritis progression, and suggesting a therapeutic approach in RA. |
| first_indexed | 2024-04-09T14:07:05Z |
| format | Article |
| id | doaj.art-e8297047994749859429bae8fb61939d |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T14:07:05Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-e8297047994749859429bae8fb61939d2023-05-07T04:17:30ZengElsevieriScience2589-00422023-05-01265106734Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritisQi-Quan Huang0Yiwei Hang1Renee Doyle2Qinwen Mao3Deyu Fang4Richard M. Pope5Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60091, USADepartment of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60091, USADepartment of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60091, USADepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USADepartments of Pathology and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60091, USADepartment of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60091, USA; Corresponding authorSummary: T regulatory cells (Tregs) are a potential therapeutic target in many autoimmune diseases including rheumatoid arthritis (RA). The mechanisms responsible for the maintenance of Tregs in chronic inflammatory conditions such as RA are poorly understood. We employed our mouse model of RA in which, the following deletion of Flice-like inhibitory protein in CD11c+ cells, CD11c-FLIP-KO (HUPO) mice develop spontaneous, progressive, erosive arthritis, with reduced Tregs, and the adoptive transfer of Tregs ameliorates the arthritis. HUPO thymic Treg development was normal, but peripheral of Treg Foxp3 was diminished mediated by reduction of dendritic cells and interleukin-2 (IL-2). During chronic inflammatory arthritis Tregs fail to maintain Foxp3, leading to non-apoptotic cell death and conversion to CD4+CD25+Foxp3- cells. Treatment with IL-2 increased Tregs and ameliorated the arthritis. In summary, reduced dendritic cells and IL-2 in the milieu of chronic inflammation, contribute to Treg instability, promoting HUPO arthritis progression, and suggesting a therapeutic approach in RA.http://www.sciencedirect.com/science/article/pii/S2589004223008118Immunology |
| spellingShingle | Qi-Quan Huang Yiwei Hang Renee Doyle Qinwen Mao Deyu Fang Richard M. Pope Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis iScience Immunology |
| title | Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis |
| title_full | Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis |
| title_fullStr | Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis |
| title_full_unstemmed | Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis |
| title_short | Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis |
| title_sort | mechanisms regulating the loss of tregs in hupo mice that develop spontaneous inflammatory arthritis |
| topic | Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223008118 |
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