Diacylglycerol kinase ζ deficiency triggers early signs of aplastic anemia in mice [article]

Miguel Martin-Salgado, Elena Andrada, Rosa Liebana, Mercedes Lopez-Santalla, Isabel Merida
2020 bioRxiv   pre-print
Diacylglycerol kinase ζ (DGKζ) limits T cell responses through phosphorylation of diacylglycerol into phosphatidic acid. This reaction attenuates diacylglycerol-dependent activation of the Ras/ERK/CD69 and PKCθ/NFκB pathways in response to antigen. Here we show that, in contrast to the lack of basal activation observed in peripheral lymphoid organs, DGKζ-/- mice showed increased numbers of activated T cells in BM, together with a significant increase in IFNγ& as well as perforin and granzyme B
more » ... rin and granzyme B and C levels. The enhanced presence of T cells in DGKζ-/- mouse BM correlates with reduced BM cellularity, impaired hematopoiesis, and lower frequency of circulating red cells, granulocytes, and platelets. Our studies coincide with the recent characterization of lower DGKζ expression in T cells isolated from the BM of patients with acquired AA, and suggest that limited DGKζ expression and/or functions predispose to T cell-mediated BM destruction. This study identifies the BM as a niche particularly sensitive to DGKζ deficiency and indicates that this mouse model could be of interest for studying the mechanism that contributes to AA development.
doi:10.1101/2020.06.05.136390 fatcat:oi2xaqt66zgcfp75csxl4t3nzq