| First Author | Mellouk A | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 957008 | PubMed ID | 36248812 |
| Mgi Jnum | J:330887 | Mgi Id | MGI:7365822 |
| Doi | 10.3389/fimmu.2022.957008 | Citation | Mellouk A, et al. (2022) P2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis. Front Immunol 13:957008 |
| abstractText | The severe lymphoproliferative and lupus diseases developed by MRL/lpr mice depend on interactions between the Fas (lpr) mutation and MRL genetic background. Thus, the Fas (lpr) mutation causes limited disease in C57BL/6 mice. We previously found that accumulating B220(+) CD4(-)CD8(-) double negative (DN) T cells in MRL/lpr mice show defective P2X7 receptor ( P2X7)-induced cellular functions, suggesting that P2X7 contributes to T-cell homeostasis, along with Fas. Therefore, we generated a B6/lpr mouse strain (called B6/lpr-p2x7KO) carrying homozygous P2X7 knockout alleles. B6/lpr-p2x7KO mice accumulated high numbers of FasL-expressing B220(+) DN T cells of CD45RB(high)CD44(high) effector/memory CD8(+) T-cell origin and developed severe lupus, characterized by leukocyte infiltration into the tissues, high levels of IgG anti-dsDNA and rheumatoid factor autoantibodies, and marked cytokine network dysregulation. B6/lpr-p2x7KO mice also exhibited a considerably reduced lifespan. P2X7 is therefore a novel regulator of T-cell homeostasis, of which cooperation with Fas is critical to prevent lymphoaccumulation and autoimmunity. |
