Role of regulatory T cells in irinotecan-induced intestinal mucositis
| Autor: | Camila Meireles de Souza Silva, Renata Brito Falcão, Paulo Roberto Carvalho Almeida, Lilia Maria Carneiro Câmara, Marcellus H.L.P. Souza, Carlos W. S. Wanderley, André George Ferreira Cândido, Camila Fernandes, Roberto C. P. Lima-Júnior, Nathália Ribeiro Pinho Souza, Heitor Amorim Muniz, Maraiza Alves Teixeira |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Linfócitos T Reguladores
Diarrhea Mucositis 0301 basic medicine medicine.medical_treatment Pharmaceutical Science chemical and pharmacologic phenomena Irinotecan T-Lymphocytes Regulatory Flow cytometry Mice 03 medical and health sciences 0302 clinical medicine Ileum medicine Animal mortality Animals Intestinal Mucosa Cyclophosphamide Peroxidase Inflammation Chemotherapy Mucosite biology medicine.diagnostic_test business.industry Acquired immune system medicine.disease Mice Inbred C57BL 030104 developmental biology Neutrophil Infiltration 030220 oncology & carcinogenesis Myeloperoxidase Immunology biology.protein Cytokines Th17 Cells Camptothecin business Infiltration (medical) medicine.drug |
| Zdroj: | Repositório Institucional da Universidade Federal do Ceará (UFC) Universidade Federal do Ceará (UFC) instacron:UFC |
| ISSN: | 0928-0987 |
| Popis: | Intestinal mucositis (IM) is a common side effect of irinotecan-based chemotherapy. The involvement of inflammatory mediators, such as TNF-α, IL1-β, IL-18 and IL-33, has been demonstrated. However, the role of adaptive immune system cells, whose activation is partially regulated by these cytokines, is yet unknown. Thus, we investigated the role of regulatory T cells (Tregs) in irinotecan-induced IM. C57BL/6 mice were injected with saline or irinotecan (75 mg kg− 1, i.p.), once a day for 4 days, and euthanized at day 1, 3, 5 or 7 following the first dose of irinotecan. For Treg depletion, the mice were pretreated with a low single dose of cyclophosphamide (100 mg kg− 1, i.p). Intestinal lamina propria lymphocytes were harvested and purified by Percoll gradient. Treg and Th17 cells were identified by flow cytometry. Blood leukocyte count was obtained and ileum samples were collected for histopathological analysis and myeloperoxidase assay. IM caused an accumulation of Tregs and Th17 cells over time. Treg depletion exacerbated intestinal damage, diarrhea, neutrophil infiltration and animal mortality, despite a reduction in Th17 cell number. The frequency of other Th cells increased and was positively correlated with neutrophil infiltration. Tregs showed a negative correlation with neutrophils and the frequency of non-regulatory Th cells. In conclusion, Tregs are important in the control of intestinal damage induced by irinotecan, and their depletion showed a deleterious effect on IM. Activation of these cells appears to be a compensatory mechanism for intestinal inflammation. |
| Databáze: | OpenAIRE |
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