LRP1-Deficient T Cells Protect Against Acute Graft Versus Host Disease in MHC-Mismatched Mice

Multi-faceted role of LRP1 in the immune system

“…Our findings show that interaction of LRP1 on T cells with membrane-bound Proteinase 3 (mP3) on neutrophils or AML in ex vivo settings leads to inhibition of T cell proliferation, suggesting that LRP1 is directly involved in T cell proliferation ( 12 ). Our preliminary findings in MHC-mismatched induced GVHD mouse models show that LRP1- deficient T cells fail to trigger GVHD in recipient mice, also suggesting an important role of LRP1 in T cell function ( 13 ). Overall, we believe that there is a lack of knowledge on LRP1 biology in various immune cell compartments.…”

“…We generated a conditional T cell specific deletion of LRP1 (LRP1 fx/fx LckCre + ) mice to investigate the capacity of LRP1 in regulating T cell proliferation in vivo ( 13 ). LRP1-deficient T cell development is overall normal in the thymus, spleen, lymph node and blood, including no significant differences in naïve, memory, or effector subsets compared to control T cells from WT mice (LRP1 fx/fx ).…”

“…The numbers of donor-derived cells and CD8 T cell subset were reduced in the spleen of recipient mice; while the percentage of naïve T cells (CD62L + CD44 + ) including both CD4 and CD8 subsets, and Tregs were increased. In addition, proinflammatory cytokines such as TNFα, IL17, IFNγ and IL2 were decreased in the serum of these recipient mice ( 13 ). The data support a novel role for LRP1 as a potential target for regulating T cell function and preventing GVHD.…”

“…Recently, we report that LRP1 plays an important role in human T cell proliferation, and leukemia associated antigen Proteinase 3 can modulate immunity via direct interaction with LRP1 on T cells ( 12 ). Furthermore, we found a novel role for LRP1 in mouse model of GVHD, and T cells deficient in LRP1 results in tolerance with incomplete donor chimerism and prevention of GVHD ( 13 ).…”