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Treatment of Intestinal Inflammation With Epicutaneous Immunotherapy Requires TGF-β and IL-10 but Not Foxp3+ Tregs
- Source :
- Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Background: Inflammatory bowel disease (IBD) involves an increase in T effector cells in the intestines that disrupts the normal balance with T regulatory cells (Tregs). A therapy that restores this balance has the potential to treat IBD. We have shown that epicutaneous exposure to OVA induces Tregs that are able to induce tolerance. The Tregs also migrate to the intestines where they alleviate colitis in mice, demonstrating the potential for skin induced Tregs to treat intestinal inflammation. We investigated the role of Foxp3, IL-10, and TGF-β in the suppression of colitis by epicutaneous immunotherapy (ET).Methods: RAG1−/− mice were transferred with CD4+CD45RBhi T cells from wild type mice to induce colitis. To determine whether Foxp3+ Tregs, IL-10-, or TGF-β-producing Tregs were necessary, Foxp3-DTR, IL-10−/−, or CD4-dnTGFBRII mice were immunized with OVA and OVA TCR enriched T cells were added. As control groups, some mice were given OVA TCR enriched T cells from wild type mice or no OVA TCR enriched T cells. Half of the mice in each group were then exposed on the skin to Viaskin patches containing OVA weekly for 3 weeks. Mice given OVA TCR enriched T cells from Foxp3-DTR mice were given diphtheria toxin (DT) or not in addition to ET. Mice were assessed for weight loss, colon length, colonic cytokine production, and histological inflammation.Results: ET, after injection with OVA TCR enriched T cells derived from wild type mice, prevented weight loss, decreased colonic inflammatory cytokine production and histological colitis. ET in the absence of the OVA TCR enriched T cells did not alleviate colitis. ET, after injection with OVA TCR enriched T cells derived from Foxp3-DTR mice, prevented weight loss, decreased colonic inflammatory cytokine production, and histological colitis. Ablation with DT did not impair the ability of ET to alleviate colitis. ET failed to alleviate colitis when OVA TCR enriched T cells were derived from IL-10−/− or CD4-dnTGFBRII mice.Conclusions: ET through induction of Tregs, which produce IL-10 and TGF-β, could be a promising treatment for IBD.
- Subjects :
- 0301 basic medicine
lcsh:Immunologic diseases. Allergy
epicutaneous immunotherapy
Ovalbumin
colitis
medicine.medical_treatment
IBD
Immunology
Inflammation
chemical and pharmacologic phenomena
Immunotherapy, Adoptive
T-Lymphocytes, Regulatory
Inflammatory bowel disease
regulatory T cells
Transforming Growth Factor beta1
Mice
03 medical and health sciences
0302 clinical medicine
Animals
Medicine
Immunology and Allergy
Diphtheria Toxin
Colitis
Original Research
Mice, Knockout
tolerance
business.industry
T-cell receptor
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Immunotherapy
Inflammatory Bowel Diseases
medicine.disease
Interleukin-10
Intestines
Mice, Inbred C57BL
Interleukin 10
030104 developmental biology
Cytokine
030211 gastroenterology & hepatology
immunotherapy
medicine.symptom
business
lcsh:RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....9b96abb9d6a5980ba1c53fc8b0da1c86
- Full Text :
- https://doi.org/10.3389/fimmu.2021.637630