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Yang G, Song W, Xu J, et al. Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production. Cell Mol Immunol. 2020;18(8):2024-2039doi: 10.1038/s41423-020-00589-1.
Yang, G., Song, W., Xu, J., Postoak, J. L., Cheng, F., Martinez, J., Zhang, J., Wu, L., & Van Kaer, L. (2021). Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production. Cellular & molecular immunology, 18(8), 2024-2039. https://doi.org/10.1038/s41423-020-00589-1
Yang, Guan, et al. "Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production." Cellular & molecular immunology vol. 18,8 (2021): 2024-2039. doi: https://doi.org/10.1038/s41423-020-00589-1
Yang G, Song W, Xu J, Postoak JL, Cheng F, Martinez J, Zhang J, Wu L, Van Kaer L. Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production. Cell Mol Immunol. 2021 Aug;18(8):2024-2039. doi: 10.1038/s41423-020-00589-1. Epub 2020 Nov 24. PMID: 33235386; PMCID: PMC8322046.
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Cell Mol Immunol. 2021 Aug;18(8):2024-2039. doi: 10.1038/s41423-020-00589-1. Epub 2020 Nov 24.

Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production.

Cellular & molecular immunology

Guan Yang, Wenqiang Song, Jielin Xu, J Luke Postoak, Feixiong Cheng, Jennifer Martinez, Jianhua Zhang, Lan Wu, Luc Van Kaer

Affiliations

  1. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
  2. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
  3. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
  4. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
  5. Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, 27709, USA.
  6. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
  7. Birmingham Veterans Affairs Medical Center, Birmingham, AL, 35233, USA.
  8. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. [email protected].

PMID: 33235386 PMCID: PMC8322046 DOI: 10.1038/s41423-020-00589-1

Abstract

The PIK3C3/VPS34 subunit of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex plays a role in both canonical and noncanonical autophagy, key processes that control immune-cell responsiveness to a variety of stimuli. Our previous studies found that PIK3C3 is a critical regulator that controls the development, homeostasis, and function of dendritic and T cells. In this study, we investigated the role of PIK3C3 in myeloid cell biology using myeloid cell-specific Pik3c3-deficient mice. We found that Pik3c3-deficient macrophages express increased surface levels of major histocompatibility complex (MHC) class I and class II molecules. In addition, myeloid cell-specific Pik3c3 ablation in mice caused a partial impairment in the homeostatic maintenance of macrophages expressing the apoptotic cell uptake receptor TIM-4. Pik3c3 deficiency caused phenotypic changes in myeloid cells that were dependent on the early machinery (initiation/nucleation) of the classical autophagy pathway. Consequently, myeloid cell-specific Pik3c3-deficient animals showed significantly reduced severity of experimental autoimmune encephalomyelitis (EAE), a primarily CD4

© 2020. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.

Keywords: Autophagy; Experimental autoimmune encephalomyelitis; IL-1β; Myeloid cells; PIK3C3

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