Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life
Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.603059/full |
| _version_ | 1818932083469320192 |
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| author | Kathryn A. Knoop Kathryn A. Knoop Keely G. McDonald Chyi-Song Hsieh Phillip I. Tarr Phillip I. Tarr Rodney D. Newberry |
| author_facet | Kathryn A. Knoop Kathryn A. Knoop Keely G. McDonald Chyi-Song Hsieh Phillip I. Tarr Phillip I. Tarr Rodney D. Newberry |
| author_sort | Kathryn A. Knoop |
| collection | DOAJ |
| description | Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development of a balanced immune system and protects against immunopathology, it remains unclear if Tregs that develop in early life continue to restrain systemic inflammatory responses throughout adulthood. Here, an inducible deletion strategy was used to label Tregs at specified time points with a targeted mechanism to be deleted later. Deletion of the Tregs labeled peri-weaning at day of life 24, but not before weaning at day of life 14, resulted in increased circulating IgE and IL-13, and abrogated induction of tolerance towards new antigens. Thus, Tregs developing peri-weaning, but not before day of life 14 are continually required to restrain allergic responses into adulthood. |
| first_indexed | 2024-12-20T04:26:51Z |
| format | Article |
| id | doaj.art-3b93539fa77a4646b74b6c35d42c8dfc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T04:26:51Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3b93539fa77a4646b74b6c35d42c8dfc2022-12-21T19:53:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.603059603059Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in LifeKathryn A. Knoop0Kathryn A. Knoop1Keely G. McDonald2Chyi-Song Hsieh3Phillip I. Tarr4Phillip I. Tarr5Rodney D. Newberry6Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Immunology, Mayo Clinic, Rochester, MN, United StatesDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Pediatrics and Molecular Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United StatesAtopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development of a balanced immune system and protects against immunopathology, it remains unclear if Tregs that develop in early life continue to restrain systemic inflammatory responses throughout adulthood. Here, an inducible deletion strategy was used to label Tregs at specified time points with a targeted mechanism to be deleted later. Deletion of the Tregs labeled peri-weaning at day of life 24, but not before weaning at day of life 14, resulted in increased circulating IgE and IL-13, and abrogated induction of tolerance towards new antigens. Thus, Tregs developing peri-weaning, but not before day of life 14 are continually required to restrain allergic responses into adulthood.https://www.frontiersin.org/articles/10.3389/fimmu.2020.603059/fullregulatory T cellsRORγTFoxp3weaningallergy |
| spellingShingle | Kathryn A. Knoop Kathryn A. Knoop Keely G. McDonald Chyi-Song Hsieh Phillip I. Tarr Phillip I. Tarr Rodney D. Newberry Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life Frontiers in Immunology regulatory T cells RORγT Foxp3 weaning allergy |
| title | Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life |
| title_full | Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life |
| title_fullStr | Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life |
| title_full_unstemmed | Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life |
| title_short | Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life |
| title_sort | regulatory t cells developing peri weaning are continually required to restrain th2 systemic responses later in life |
| topic | regulatory T cells RORγT Foxp3 weaning allergy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.603059/full |
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