PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model
| Autor: | Hila Ben-Yehuda, Ido Amit, Hadas Keren-Shaul, Neta Rosenzweig, Kuti Baruch, Assaf Weiner, Michal Schwartz, Liora Cahalon, Afroditi Tsitsou-Kampeli, Raz Dvir-Szternfeld, Pierre Weill-Raynal, Alex Kertser |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Amyloid beta medicine.medical_treatment Science Programmed Cell Death 1 Receptor General Physics and Astronomy Mice Inbred Strains Mice Transgenic 02 engineering and technology Article B7-H1 Antigen General Biochemistry Genetics and Molecular Biology MSR1 03 medical and health sciences Immune system Alzheimer Disease PD-L1 medicine Animals Humans Cognitive Dysfunction lcsh:Science Antibodies Blocking Receptor Mice Inbred BALB C Multidisciplinary biology business.industry Macrophages Brain General Chemistry Immunotherapy 021001 nanoscience & nanotechnology medicine.disease Immune checkpoint 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology Tauopathies biology.protein Cancer research lcsh:Q Tauopathy 0210 nano-technology business |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Alzheimer’s disease (AD) is a heterogeneous disorder with multiple etiologies. Harnessing the immune system by blocking the programmed cell death receptor (PD)-1 pathway in an amyloid beta mouse model was shown to evoke a sequence of immune responses that lead to disease modification. Here, blocking PD-L1, a PD-1 ligand, was found to have similar efficacy to that of PD-1 blocking in disease modification, in both animal models of AD and of tauopathy. Targeting PD-L1 in a tau-driven disease model resulted in increased immunomodulatory monocyte-derived macrophages within the brain parenchyma. Single cell RNA-seq revealed that the homing macrophages expressed unique scavenger molecules including macrophage scavenger receptor 1 (MSR1), which was shown here to be required for the effect of PD-L1 blockade in disease modification. Overall, our results demonstrate that immune checkpoint blockade targeting the PD-1/PD-L1 pathway leads to modification of common factors that go awry in AD and dementia, and thus can potentially provide an immunotherapy to help combat these diseases. Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy. The authors show here that blocking PD-L1, a PD-1 ligand, is similarly effective, and that both treatments reversed cognitive deficiencies, and modified disease pathology not only in an animal model of AD, but also in the DM-hTAU mouse tauopathy model, through a mechanism that involves monocyte-derived macrophages. |
| Databáze: | OpenAIRE |
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