P2X7 receptor knockout prevents streptozotocin-induced type 1 diabetes in mice.
Type 1 diabetes (T1D) is caused by autoimmune destruction of islet of Langerhans β-cells. P2X7 receptors (P2X7R) modulate proinflammatory immune responses by binding extracellular ATP, a classic 'danger signal'. Here, we evaluated whether the P2X7R has a role in T1D development. P2X7(-/-) mice are resistant to TD1 induction by streptozotocin (STZ) treatment, with no increase in blood glucose, decrease in insulin-positive cells, and pancreatic islet reduction, compared to WT (C57BL/6) mice. Also, the levels of proinflammatory mediators (IL-1β, IFN-γ and NO) did not increase after STZ treatment in P2X7(-/-) animals, with reduced infiltration of CD4(+), CD8(+), B220(+), CD11b(+) and CD11c(+) cells in the pancreatic lymph nodes. Treatment with a P2X7 antagonist mimicked the effect of P2X7 knockout, preventing STZ-induced diabetes. Our results show that the absence of the P2X7R provides resistance in the induction of diabetes in this model, and suggest that therapy targeting the P2X7R may be useful against clinical T1D.
Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Flávia Sarmento
FS
Vieira
Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Hayandra Ferreira
HF
Nanini
Laboratório de Patologia Clínica do Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, CCS, Rio de Janeiro, RJ, Brazil.
Christina Maeda
CM
Takiya
Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: rcsilva@biof.ufrj.br.
Robson
R
Coutinho-Silva
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D055786:Gene Knockout Techniques; D007515:Islets of Langerhans / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*; D013311:Streptozocin
D001786:Blood Glucose; D016207:Cytokines; D058486:Receptors, Purinergic P2X7; D009569:Nitric Oxide; D013311:Streptozocin
Islet of Langerhans; P2X7 receptor; Type 1 diabetes; eATP