Tbet Expression in Regulatory T Cells Is Required to Initiate Th1-Mediated Colitis
| Autor: | Carmine Stolfi, Giovanni Monteleone, Federica Facciotti, Massimo Fantini, Flavio Caprioli, Sara Onali, Hans-Joerg Fehling, Martina Di Giovangiulio, Agnese Favale, Angelamaria Rizzo, Eleonora Franzè |
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| Přispěvatelé: | Di Giovangiulio, M, Rizzo, A, Franzè, E, Caprioli, F, Facciotti, F, Onali, S, Favale, A, Stolfi, C, Fehling, H, Monteleone, G, Fantini, M |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Male Adoptive cell transfer Immunology chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Interleukin 22 Treg cells Tbet Th1-like Tregs inflammatory bowel disease inflammation 03 medical and health sciences Mice 0302 clinical medicine Immune system Th1-like Tregs inflammatory bowel disease Conditional gene knockout Immunology and Allergy Animals Humans Original Research Settore MED/12 - Gastroenterologia Settore BIO/12 FOXP3 Tbet Treg cells inflammation hemic and immune systems Th1 Cells Colitis Inflammatory Bowel Diseases Interleukin 10 030104 developmental biology Gene Expression Regulation Interleukin 12 Female Interleukin 17 lcsh:RC581-607 T-Box Domain Proteins 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
| ISSN: | 1664-3224 |
| Popis: | In normal conditions gut homeostasis is maintained by the suppressive activity of regulatory T cells (Tregs), characterized by the expression of the transcription factor FoxP3. In human inflammatory bowel disease, which is believed to be the consequence of the loss of tolerance toward antigens normally contained in the gut lumen, Tregs have been found to be increased and functionally active, thus pointing against their possible role in the pathogenesis of this immune-mediated disease. Though, in inflammatory conditions, Tregs have been shown to upregulate the T helper (Th) type 1-related transcription factor Tbet and to express the pro-inflammatory cytokine IFN gamma, thus suggesting that at a certain point of the inflammatory process, Tregs might contribute to inflammation rather than suppress it. Starting from the observation that Tregs isolated from the lamina propria of active but not inactive IBD patients or uninflamed controls express Tbet and IFN gamma, we investigated the functional role of Th1-like Tregs in the dextran sulfate model of colitis. As observed in human IBD, Th1-like Tregs were upregulated in the inflamed lamina propria of treated mice and the expression of Tbet and IFN gamma in Tregs preceded the accumulation of conventional Th1 cells. By using a Treg-specific Tbet conditional knockout, we demonstrated that Tbet expression in Tregs is required for the development of colitis. Indeed, Tbet knockout mice developed milder colitis and showed an impaired Th1 immune response. In these mice not only the Tbet deficient Tregs but also the Tbet proficient conventional T cells showed reduced IFN gamma expression. However, Tbet deficiency did not affect the Tregs suppressive capacity in vitro and in vivo in the adoptive transfer model of colitis. In conclusion here we show that Tbet expression by Tregs sustains the early phase of the Th1-mediated inflammatory response in the gut. |
| Databáze: | OpenAIRE |
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