Background: The use of immature dendritic cells (imDCs) to induce
donor-specific immunotolerance following in vivo stimulation is limited
by their low rate of induction and their tendency to undergo maturation. We
derived imDCs from bone marrow hematopoietic stem cells (HSCs-imDCs). We then
tested the ability of naringenin (Nar) to impede the maturation of HSCs-imDCs for
inducing transplantation immune tolerance. Methods: HSCs derived from
bone marrow were collected and induced to differentiate into imDCs by treating
with Nar (Nar-HSCs-imDCs). Flow cytometry was used to evaluate DC surface
markers, apoptosis, and endocytic ability. The ability of DCs to influence the
in vitro proliferation of T cells and of regulatory T cells (Tregs) was
analyzed by mixed lymphocyte reaction assays. Enzyme-linked immunoassays were
used to quantify cytokine levels in supernatants from co-cultured DCs and Tregs,
as well as in the serum of experimental animals. The level of immunotolerance
induced by Nar-HSCs-imDCs was evaluated by skin grafting in recipient Balb/c
mice, while the Kaplan-Meier method was used to statistically evaluate graft
survival. Results: Compared with HSC-imDCs, Nar-HSCs-imDCs showed higher
expression of cluster of differentiation 11c (CD11c), but lower expression levels
of CD80, CD86, and major histocompatibility complex class II. Nar-HSCs-imDCs also
showed stronger inhibition of T cells and higher Treg cell proliferation.
Interleukin 2 (IL-2) and interferon gamma levels were downregulated in
Nar-HSCs-imDCs, whereas IL-4, IL-10, and transforming growth factor beta levels
were upregulated. The rate of apoptosis and endocytic capacity of Nar-HSCs-DCs
increased significantly after treatment with lipopolysaccharide. HSCs-imDCs or
Nar-HSCs-imDCs were injected into Balb/c mice via the tail vein 7 days before
skin grafting. Significantly reduced donor-specific CD4
Announcements
Open Access
Original Research
Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival
Puxun Tian1,2, Xiaoyan Huang1, Kun Zhu3, Zhankui Jin1, Yan Li1, Bingxuan Zheng1, Xiangrong Zhao1, Yangmeng Feng1, Qing Feng1, Dongliang Li1, Jiaojiao Wang1, Cuixiang Xu1,*
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1
Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China
2
Institute of Organ Transplantation, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China
3
Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, 710061 Xi'an, Shaanxi, China
*Correspondence: xucuixiang1129@163.com (Cuixiang Xu)
Front. Biosci. (Landmark Ed) 2023, 28(5), 91;
https://doi.org/10.31083/j.fbl2805091
Submitted: 22 November 2022 | Revised: 14 March 2023 | Accepted: 23 March 2023 | Published: 11 May 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract
Keywords
naringenin
hematopoietic stem cells
immature dendritic cells
immune tolerance
skin graft
Funding
2021BJ-07/Technology Talent Support Program of Shaanxi Provincial People’s Hospital
81900686/National Natural Science Foundation of China
21JS038/Key Projects of Shaanxi Provincial Department of Education
2020YXM-08/Science and Technology Incubation Fund Project of Shaanxi Provincial People’s Hospital
2021ZDLSF01-07/Shaanxi Province Key R&D Project
Figures
Fig. 1.