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  Repression of phagocytosis by human CD33 is not conserved with mouse CD33

Bhattacherjee, A., Rodrigues, E., Jung, J., Luzentales-Simpson, M., Enterina, J. R., Galleguillos, D., et al. (2019). Repression of phagocytosis by human CD33 is not conserved with mouse CD33. Communications Biology, 2: 450. doi:10.1038/s42003-019-0698-6.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-5457-B Version Permalink: http://hdl.handle.net/21.11116/0000-0005-85D4-5
Genre: Journal Article

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 Creators:
Bhattacherjee, Abhishek, Author
Rodrigues, Emily, Author
Jung, Jaesoo, Author
Luzentales-Simpson, Matthew, Author
Enterina, Jhon R., Author
Galleguillos, Danny, Author
Laurent, St., Author
D., Chris, Author
Nakhaei-Nejad, Maryam, Author
Fuchsberger, Felix F.1, Author              
Streith, Laura, Author
Wang, Qian, Author
Kawasaki, Norihito, Author
Duan, Shiteng, Author
Bains, Arjun, Author
Paulson, James C., Author
Rademacher, Christoph1, Author              
Giuliani, Fabrizio, Author
Sipione, Simonetta, Author
Macauley, Matthew S., Author
Affiliations:
1Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863300              

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Free keywords: Microglia; Neuroimmunology
 Abstract: CD33 is an immunomodulatory receptor linked to Alzheimer’s disease (AD) susceptibility via regulation of phagocytosis in microglia. Divergent features between human CD33 (hCD33) and murine CD33 (mCD33) include a unique transmembrane lysine in mCD33 and cytoplasmic tyrosine in hCD33. The functional consequences of these differences in restraining phagocytosis remains poorly understood. Using a new αmCD33 monoclonal antibody, we show that mCD33 is expressed at high levels on neutrophils and low levels on microglia. Notably, cell surface expression of mCD33 is entirely dependent on Dap12 due to an interaction with the transmembrane lysine in mCD33. In RAW264.7 cultured macrophages, BV-2 cultured microglia, primary neonatal and adult microglia, uptake of cargo — including aggregated Aβ1–42 — is not altered upon genetic ablation of mCD33. Alternatively, deletion of hCD33 in monocytic cell lines increased cargo uptake. Moreover, transgenic mice expressing hCD33 in the microglial cell lineage showed repressed cargo uptake in primary microglia. Therefore, mCD33 and hCD33 have divergent roles in regulating phagocytosis, highlighting the importance of studying hCD33 in AD susceptibility.

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Language(s): eng - English
 Dates: 2019-12-032019
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s42003-019-0698-6
BibTex Citekey: Bhattacherjee2019
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Title: Communications Biology
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 2 Sequence Number: 450 Start / End Page: - Identifier: ISSN: 2399-3642

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Title: Communications Biology
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 3 Sequence Number: 36 Start / End Page: - Identifier: ISSN: 2399-3642