The Effects of 1,25( OH ) 2D3 treatment on Immune Responses and Intracellular Metabolic Pathways of Bone Marrow‐Derived Dendritic Cells from Lean and Obese Mice

IUBMB Life ◽  
2021 ◽  
Author(s):  
Da Hye Cho ◽  
Ga Young Lee ◽  
Jeong Hee An ◽  
Sung Nim Han
Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5875-5884 ◽  
Author(s):  
Hideaki Tanizaki ◽  
Gyohei Egawa ◽  
Kayo Inaba ◽  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
...  

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.


2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Ken-Zaburo Oshima ◽  
Kazuhito Asano ◽  
Ken-Ichi Kanai ◽  
Miyuki Suzuki ◽  
Harumi Suzaki

There is established concept that dendritic cells (DCs) play essential roles in the development of allergic immune responses. However, the influence of receptor antagonists on DC functions is not well defined. The aim of the present study was to examine the effect of epinastine hydrochloride (EP), the most notable histamine receptor antagonists in Japan, onDermatophagoides farinae (Der f)-pulsed mouse bone marrow-derived DCs in vitro and in vivo. EP at more than 25 ng/mL could significantly inhibit the production of IL-6, TNF- and IL-10 fromDer f-pulsed DCs, which was increased byDer fchallenge in vitro. On the other hand, EP increased the ability ofDer f-pulsed DCs to produce IL-12. Intranasal instillation ofDer f-pulsed DCs resulted in nasal eosinophilia associated with a significant increase in IL-5 levels in nasal lavage fluids.Der f-pulsed and EP-treated DCs significantly inhibited nasal eosinophila and reduced IL-5. These results indicate that EP inhibits the development of Th2 immune responses through the modulation of DC functions and results in favorable modification of clinical status of allergic diseases.


Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 161 ◽  
Author(s):  
Lonneke V. Nouwen ◽  
Bart Everts

Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role of mTOR in controlling metabolism and DC and macrophage function, pathogens have evolved strategies to target this pathway to manipulate these cells. This review seeks to discuss the most recent insights into how pathogens target DC and macrophage metabolism to subvert potential deleterious immune responses against them, by focusing on the metabolic pathways that are known to regulate and to be regulated by mTOR signaling including amino acid, lipid and carbohydrate metabolism, and autophagy.


2004 ◽  
Vol 78 (20) ◽  
pp. 11152-11160 ◽  
Author(s):  
Rongcun Yang ◽  
Francisco Martinez Murillo ◽  
Hengmi Cui ◽  
Richard Blosser ◽  
Satoshi Uematsu ◽  
...  

ABSTRACT Dendritic cells (DCs) link innate and adaptive immunity by sensing pathogens or vaccinogens and signaling a variety of defense responses. Since human papillomavirus type 16 L1 virus-like particles (HPV16 VLPs) induce a potent, protective immune response after vaccination, we examined their recognition by DCs. HPV16 VLPs cause phenotypic maturation of murine bone marrow-derived DCs (BMDCs), and immunization of mice with HPV16 VLP-loaded BMDCs or HPV16 VLPs alone induced T helper 1 (Th1)-biased immune responses. Analysis of transcriptional responses of murine BMDCs by microarray suggested that alpha/beta interferon (IFN-α/β) transcripts and numerous proinflammatory cytokines and chemokines are up regulated in response to HPV16 VLPs. Indeed, the induction of IFN-α, IFN-γ, and interleukin-12 (IL-12) production by BMDCs after stimulation with HPV16 VLPs was demonstrated by quantitative enzyme-linked immunosorbent assay. Many microbial products that induce proinflammatory responses are recognized via Toll-like receptor (TLR) signaling through the key adaptor protein MyD88 and activation of NF-κB, nuclear factor of activated T cells (NF-AT), and activating protein 1 (AP-1). Reporter assays indicated that HPV16 VLPs activated NF-κB-, NF-AT-, and AP-1-dependent transcription in the RAW264.7 macrophage cell line. Knockdown of MyD88 transcripts by small interfering RNA in the RAW264.7 macrophage cell line inhibited the activation of NF-κB-, NF-AT- and AP-1-dependent transcription by HPV16 VLP. Furthermore, MyD88−/− BMDCs failed to up regulate IL-12 and IFN-α and -γ in response to HPV16 VLPs. Finally, Th1-biased immune responses to HPV16 VLPs are dramatically impaired in MyD88 and IFN-α/β receptor-deficient mice. This implicates TLR recognition as central to immune recognition of HPV16 L1 VLPs.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robin H. G. A. van den Biggelaar ◽  
Larissa van der Maas ◽  
Hugo D. Meiring ◽  
Jeroen L. A. Pennings ◽  
Willem van Eden ◽  
...  

AbstractInactivated poultry vaccines are subject to routine potency testing for batch release, requiring large numbers of animals. The replacement of in vivo tests for cell-based alternatives can be facilitated by the identification of biomarkers for vaccine-induced immune responses. In this study, chicken bone marrow-derived dendritic cells were stimulated with an inactivated vaccine for infectious bronchitis virus and Newcastle disease virus, as well as inactivated infectious bronchitis virus only, and lipopolysaccharides as positive control, or left unstimulated for comparison with the stimulated samples. Next, the cells were lysed and subjected to proteomic analysis. Stimulation with the vaccine resulted in 66 differentially expressed proteins associated with mRNA translation, immune responses, lipid metabolism and the proteasome. For the eight most significantly upregulated proteins, mRNA expression levels were assessed. Markers that showed increased expression at both mRNA and protein levels included PLIN2 and PSMB1. Stimulation with infectious bronchitis virus only resulted in 25 differentially expressed proteins, which were mostly proteins containing Src homology 2 domains. Stimulation with lipopolysaccharides resulted in 118 differentially expressed proteins associated with dendritic cell maturation and antimicrobial activity. This study provides leads to a better understanding of the activation of dendritic cells by an inactivated poultry vaccine, and identified PLIN2 and PSMB1 as potential biomarkers for cell-based potency testing.


2009 ◽  
Vol 50 ◽  
pp. S216
Author(s):  
M. Saad-Farag ◽  
B. Hoyler ◽  
J. Encke ◽  
W. Stremmel ◽  
K. Weigand

2012 ◽  
Vol 51 (1) ◽  
pp. 39
Author(s):  
Chaung Hso-Chi ◽  
Chung Wen-Bin ◽  
Chen Yu-Zhan ◽  
Wu Chang-Jer ◽  
Liu Shyh-Hwa

2007 ◽  
Vol 15 (1) ◽  
pp. 35-41 ◽  
Author(s):  
R. Keith Reeves ◽  
Patricia N. Fultz

ABSTRACT Plasmacytoid dendritic cells (pDCs), one of two types of bone marrow (BM)-derived blood DCs, play an important role in linking innate and adaptive immune responses. However, little is known about the nature of pDCs that reside in the BM. Because the simian immunodeficiency virus-macaque model closely mimics human immunodeficiency virus disease in humans, with both infections inducing a decrease in pDCs, we characterized and compared pDCs in the BM with those in peripheral blood (PB) of healthy pig-tailed macaques. The results revealed that pDCs from both compartments had the same CD123++ HLA-DR+ Lin− phenotype and were similar in size. Although BM-derived pDCs (BM-pDCs) were 3-fold greater in frequency and 10-fold greater in number, they had lower cell surface expression of both HLA-DR and the costimulatory molecule CD86 than did PB-pDCs. Both BM- and PB-pDCs responded ex vivo to synthetic CpG oligodeoxynucleotides and inactivated influenza virus by upregulating HLA-DR and CD86 and secreting cytokines; however, stimulated BM-pDCs secreted less alpha interferon and tumor necrosis factor alpha per cell than did PB-pDCs. These results suggest that while BM-pDCs appear to be phenotypically less mature than PB-pDCs, they do respond to pathogens. Thus, during acute infections, these cells could initiate immune responses either in the BM or after rapidly migrating from the BM into the periphery. A better characterization of pDCs in blood and tissues will be beneficial for future studies of macaques that focus on either pathogenesis or vaccine development.


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