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Title in Portuguese: Role of regulatory T cells in irinotecan-induced intestinal mucositis
Author: Fernandes, Camila
Wanderley, Carlos Wagner Souza
Silva, Camila Meireles Souza
Muniz, Heitor Amorim
Teixeira, Maraiza Alves
Souza, Nathália Ribeiro Pinho
Cândido, André George Ferreira
Falcão, Renata Brito
Souza, Marcellus Henrique Loiola Ponte
Almeida, Paulo Roberto Carvalho
Câmara, Lilia Maria Carneiro
Lima-Júnior, Roberto César Pereira
Keywords: Mucosite
Linfócitos T Reguladores
T-Lymphocytes, Regulatory
Issue Date: Mar-2018
Citation: FERNANDES, Camila et al. Role of regulatory T cells in irinotecan-induced intestinal mucositis. European Journal of Pharmaceutical Sciences, Amsterdam, v.115, p. 158-166, mar. 2018.
Abstract: 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.
metadata.dc.type: Artigo de Periódico
ISSN: 0928-0987
Appears in Collections:DMC - Artigos publicados em revistas científicas

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