| Autor: |
Amine Mellouk, Tom Hutteau-Hamel, Julie Legrand, Hanaa Safya, Mohcine Benbijja, Françoise Mercier-Nomé, Karim Benihoud, Jean M. Kanellopoulos, Pierre Bobé |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2022.957008 |
| Popis: |
The severe lymphoproliferative and lupus diseases developed by MRL/lpr mice depend on interactions between the Faslpr mutation and MRL genetic background. Thus, the Faslpr 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 CD45RBhighCD44high 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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