Lipopolysaccharide-Activated Bone Marrow-Derived Dendritic Cells Suppress Allergic Airway Inflammation by Ameliorating the Immune Microenvironment

Min, Zhihui; Zeng, Yuzhen; Zhu, Tao; Cui, Bo; Mao, Ruolin; Jin, Meiling; Chen, Zhihong

doi:10.3389/fimmu.2021.595369

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…Hence, we reasoned that the low number of eosinophils and low IL-5 production might be related to the inhibitory effect of the predominant Th1 immunity developed in IL-10-deficient mice. Since in vitro-generated BM-DCs have been employed to modulate allergic airway Th2 responses [37][38][39][40] as well as Th1 activities [41][42][43], we generated BM-DCs from IL-10 −/− or WT mice to address more directly the role of IL-10 on DCs. We found that sensitizations with BM-DCs from WT or IL-10 −/− mice primed with OVA could induce allergic lung inflammation after OVA challenge and that the addition of CpG-ODN prevented the development of allergic responses.…”

Section: Discussionmentioning

confidence: 99%

CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization

2021

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Allergen-specific T helper (Th)2 cells orchestrate upon allergen challenge the development of allergic eosinophilic lung inflammation. Sensitization with alum adjuvant, a type 2 adjuvant, has been used extensively in animal models of allergic lung disease. In contrast, type 1 adjuvants like CpG-ODN, a synthetic toll-like receptor 9 agonist, inhibit the development of Th2 immunity. CpG-ODN induce type 1 and suppressive cytokines that influence Th2 cell differentiation. Here, we investigated the immune modulatory effect of CpG-ODN on allergic sensitization to OVA with alum focusing on dendritic cells (DCs) expressing the MyD88 molecule and the suppressive IL-10 cytokine. Using mice with specific cell deletion of MyD88 molecule, we showed that CpG-ODN suppressed allergic sensitization and consequent lung allergic inflammation signaling through the MyD88 pathway on dendritic cells, but not on B-cells. This inhibition was associated with an increased production of IL-10 in the bronchoalveolar lavage fluid. Sensitization to OVA with CpG-ODN of IL-10-deficient, but not wild-type mice, induced a shift towards Th1 pattern of inflammation. Employing bone marrow-derived dendritic cells (BM-DCs) pulsed with OVA for sensitizations with or without CpG-ODN, we showed that IL-10 is dispensable for the inhibition of allergic lung Th2 responses by CpG-ODN. Moreover, the lack of IL-10 on DCs was not sufficient for the CpG-ODN-induced immune-deviation towards a Th1 pattern. Accordingly, we confirmed directly the role of MyD88 pathway on DCs in the inhibition of allergic sensitization.

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Section: Discussionmentioning

confidence: 99%

CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization

2021

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“…Under varying circumstances, LPS not only induces the maturation of DCs to exert immune responses but also enables DCs to initiate immunosuppressive functions (20,27). It is widely accepted that DCs acquire endotoxin tolerance after repeated exposure to sublethal LPS in vivo (20,28,29), whereas this phenomenon remains uncertain in vitro. Considering the persistent inflammation during sepsis and the potential regulatory effects of LPS, it is imperative to establish a model for inducing tolDCs through prolonged stimulation with LPS to investigate their role in chronic inflammatory pathology.…”

Section: Introductionmentioning

confidence: 99%

“…These protocols use various immunosuppressive agents, including rapamycin, dexamethasone, and vitamin D, as well as inhibitory cytokines such as IL-10 and TGF-β, to alleviate excessive and undesired immune responses (16,18,19). Furthermore, IL-10 has been identified as the most potent pharmacological agent for inducing tolDCs among these options (20,21). However, a major limitation of tolDCs is their inability to accurately represent the pathophysiology of sepsis in terms of chronic low-grade inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Lipopolysaccharide (LPS), a well-established inducer of the inflammatory cascade, exerts a potent stimulatory effect on DCs by activating toll-like receptor 4 signaling (26). Under varying circumstances, LPS not only induces the maturation of DCs to exert immune responses but also enables DCs to initiate immunosuppressive functions (20,27). It is widely accepted that DCs acquire endotoxin tolerance after repeated exposure to sublethal LPS in vivo (20,28,29), whereas this phenomenon remains uncertain in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Generation of Tolerogenic Dendritic Cells under the Persistent Inflammation Stimulation

Miao,

Chang,

et al. 2024

Shock

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Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that Interleukin-10-induced tolDCs (IL-10-tolDCs) are a well-established model, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as a promising therapeutic target for ameliorating the immunosuppressed state in septic patients.

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“…Most dendritic cells in vivo are in an immature and inactive state. Consequently, they can be converted to a mature and active state with different phenotypic and functional characteristics by exposure of these cells to different stimulatory ligands [10].…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticles Stimulate the Maturation and Activation of Mouse Bone Marrow Dendritic Cells

Aluisa¹,

Debut²,

Seqqat³

et al. 2022

Int. J. Adv. Sci. Eng. Inf. Technol.

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Nanomedicine is an interdisciplinary science that links nanotechnology, nanoscience and nanoengineering to the field of health and the use of nanoscale tools, in this case, nanoparticles have great therapeutic potential against target cells such as dendritic cells (DC). DCs are highly motile cells whose main function is antigen presentation; they are mediators between innate and adaptive immunity. In this investigation, DCs were differentiated and matured with granulocyte-macrophage colony stimulating factor (GM-CSF), 25 ug/mL and spherical gold nanoparticles (AuNPs) of approximately 30 nm at concentrations of 5 to 200 ug/mL. DCs were obtained from the bone marrow of adult mice; their characterization was performed by means of RT-PCR, scanning electron microscopy (SEM) and confocal to know their morphology and the location of the nanoparticles inside. The bone marrow DCs (bmDCs) possibly differentiated into cCD1 dendritic cells, their mature morphological status was determined by the presence of co-stimulatory factors (CD40, CD86 and CD11c), in addition to MHC II and CIITA when in contact with AuNPs, the results were confirmed by SEM observation due to their star-like shape. In terms of the location of the AuNPs they would be clustered and outside the nucleus. The discovery of nanoparticles that do not cause significant cytotoxicity, activate dendritic cells, and produce cytokines, causing phenotypic changes in them, enhancing, and modulating the adaptive immune response or generating a targeted immunotherapy in the presence of different pathogens in the organism.

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Lipopolysaccharide-Activated Bone Marrow-Derived Dendritic Cells Suppress Allergic Airway Inflammation by Ameliorating the Immune Microenvironment

Cited by 17 publications

References 41 publications

CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization

CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization

Generation of Tolerogenic Dendritic Cells under the Persistent Inflammation Stimulation

Gold Nanoparticles Stimulate the Maturation and Activation of Mouse Bone Marrow Dendritic Cells

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