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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 1364165, 9 pages
https://doi.org/10.1155/2018/1364165
Research Article

PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

1The Department of Hematology, General Hospital of Tianjin Medical University, Tianjin, China
2The Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin, China

Correspondence should be addressed to Zonghong Shao; nc.ude.umt@gnohgnozoahs

Received 26 September 2017; Revised 22 December 2017; Accepted 10 January 2018; Published 15 February 2018

Academic Editor: Massimo Collino

Copyright © 2018 Chunyan Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Severe aplastic anemia (SAA) is an autoimmune disease in which bone marrow failure is mediated by activated myeloid dendritic cells (mDCs) and T lymphocytes. Recent research has identified a strong immunomodulatory effect of pyruvate kinase M2 (PKM2) on dendritic cells in immune-mediated diseases. In this study, we aimed to explore the role of PKM2 in the activation of mDCs in SAA. We observed conspicuously higher levels of PKM2 in mDCs from SAA patients compared to normal controls at both the gene and protein levels. Concurrently, we unexpectedly discovered that after the mDC-specific downregulation of PKM2, mDCs from patients with SAA exhibited weakened phagocytic activity and significantly decreased and shortened dendrites relative to their counterparts from normal controls. The expression levels of the costimulatory molecules CD86 and CD80 were also reduced on mDCs. Our results also suggested that PKM2 knockdown in mDCs reduced the abilities of these cells to promote the activation of CD8+ T cells (CTLs), leading to the decreased secretion of cytotoxic factors by the latter cell type. These findings demonstrate that mDC activation requires an elevated intrinsic PKM2 level and that PKM2 improves the immune status of patients with SAA by enhancing the functions of mDCs and, consequently, CTLs.