Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/29544
Title: P2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells
Authors: Figliuolo, Vanessa R.
Savio, Luiz Eduardo Baggio
Safya, Hanaa
Nanini, Hayandra
Bernardazzi, Cláudio
Abalo, Alessandra
Souza, Heitor S. P. de
Kanellopoulos, Jean
Bobé, Pierre
Coutinho, Cláudia M. L. M.
Silva, Robson Coutinho
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Université Paris-Sud. Interactions Cellulaires et Physiopathologie Hépatique. Orsay, Paris / Université Paris Diderot. Centre de la recherche sur l'inflammation,. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Departamento de Clínica Médica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Departamento de Clínica Médica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Departamento de Clínica Médica. Rio de Janeiro, RJ, Brasil.
Université Paris-Sud. Centre National de la Recherche Scientifique. Institut de Biologie intégrative de la cellule. Orsay, France.
Université Paris Sud. Interactions Cellulaires et Physiopathologie Hépatique. Orsay, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Universidade Federal Fluminense. Instituto de Biologia. Niterói, RJ, Brasi
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Abstract: P2X7 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.
Keywords: ATP
P2X7 receptor
Colitis, regulatory T cells
keywords: Colite, células T reguladoras
Receptor P2X7
DeCS: Trifosfato de Adenosina
Issue Date: 2017
Publisher: Elsevier
Citation: FIGLIUOLO, 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.
DOI: 10.1016/j.bbadis.2017.03.004
ISSN: 0925-4439
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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