P2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells

dc.creatorFigliuolo, Vanessa R.
dc.creatorSavio, Luiz Eduardo Baggio
dc.creatorSafya, Hanaa
dc.creatorNanini, Hayandra
dc.creatorBernardazzi, Cláudio
dc.creatorAbalo, Alessandra Alves
dc.creatorSouza, Heitor S. P. de
dc.creatorKanellopoulos, Jean
dc.creatorBobé, Pierre
dc.creatorCoutinho, Cláudia M. L. M.
dc.creatorSilva, Robson Coutinho
dc.date2018-10-11T17:34:33Z
dc.date2018-10-11T17:34:33Z
dc.date2017
dc.date.accessioned2023-09-26T23:33:02Z
dc.date.available2023-09-26T23:33:02Z
dc.identifierFIGLIUOLO, Vanessa R. et al. P2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells. BBA - Molecular Basis of Disease, v.1863, p.1183-1194, 2017.
dc.identifier0925-4439
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/29544
dc.identifier10.1016/j.bbadis.2017.03.004
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8891777
dc.descriptionP2X7 receptor activation contributes to inflammation development in different pathologies. We previously reported that the P2X7 receptor is over-expressed in the gut mucosa of patients with inflammatory bowel disease, and that P2X7 inhibition protects against chemically induced colitis. Here, we investigated in detail the role of the P2X7 receptor in inflammatory bowel disease development, by treating P2X7 knockout (KO) and WT mice with two different (and established) colitis inductors. P2X7 KO mice were protected against gut inflammation induced by 2,4,6-trinitrobenzenesulfonic acid or oxazolone, with no weight loss or gut histological alterations after treatment. P2X7 receptor knockout induced regulatory T cell accumulation in the colon, as evaluated by qRT-PCR for FoxP3 expression and immunostaining for CD90/CD45RBlow. Flow cytometry analysis of mesenteric lymph node cells showed that P2X7 activation (by ATP) triggered regulatory T cell death. In addition, such cells from P2X7 KO mice expressed more CD103, suggesting increased migration of regulatory T cells to the colon (relative to the WT). Our results show that the P2X7 has a key role during inflammation development in inflammatory bowel disease, by triggering the death and retention in the mesenteric lymph nodes of regulatory T cells that would otherwise promote immune system tolerance in the gut.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectColite, células T reguladoras
dc.subjectReceptor P2X7
dc.subjectATP
dc.subjectP2X7 receptor
dc.subjectColitis, regulatory T cells
dc.subjectTrifosfato de Adenosina
dc.titleP2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells
dc.typeArticle


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