•Systematic lupus erythematosus (SLE) is an autoimmune disease reflecting an imbalance between effector and regulatory immune responses.•Inflammatory DCs (inflDC) can initiate and trigger lymphocyte ...responses in SLE with over-expression of surface molecules and pro-inflammatory cytokine.•Tolerogenic DCs (tolDC) express inhibitory interacting surface molecules and repressive mediators.•tolDCs can be a therapeutic candidate for patients with SLE to suppress their systematic inflammation.•Recent pre-clinical and clinical studies showed the efficacy of tolDCs therapy in autoimmune diseases, particularly SLE.
Systematic lupus erythematosus (SLE) is an autoimmune disease reflecting an imbalance between effector and regulatory immune responses. Dendritic cells (DC) are a link between innate and adaptive immunity. Inflammatory DCs (inflDC) can initiate and trigger lymphocyte responses in SLE with over-expression of surface molecules and pro-inflammatory cytokine, including Interferon (IFN) α, Interleukin (IL) 1α, IL-1β, and IL-6, resulting in the overreaction of T helper cells (Th), and B cells immune responses. On the opposite side, tolerogenic DCs (tolDC) express inhibitory interacting surface molecules and repressive mediators, such as IL-10, Transforming growth factor beta (TGF-β), and Indoleamine 2, 3-dioxygenase (IDO), which can maintain self-tolerance in SLE by induction of regulatory T cells (Treg), T cells deletion and anergy. Hence, tolDCs can be a therapeutic candidate for patients with SLE to suppress their systematic inflammation. Recent pre-clinical and clinical studies showed the efficacy of tolDCs therapy in autoimmune diseases. In this review, we provide a wide perspective on the effect of inflDCs in promoting inflammation and the role of tolDC in the suppression of immune cells’ overreaction in SLE. Furthermore, we reviewed the finding of clinical trials and experimental studies related to autoimmune diseases, particularly SLE.
Role of IL‐6 in dendritic cell functions Xu, Yu‐Dong; Cheng, Mi; Shang, Pan‐Pan ...
Journal of leukocyte biology,
March 2022, Letnik:
111, Številka:
3
Journal Article
Recenzirano
Dendritic cells (DCs) are efficient antigen‐presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in cellular and humoral immune ...responses by presenting antigens to initiate T cell reactions, cytokine and chemokine secretion, T cell differentiation and expansion, B cell activation and regulation, and the mediation of immune tolerance. The functions of DCs depend on their activation status, which is defined by the stages of maturation, phenotype differentiation, and migration ability, among other factors. IL‐6 is a soluble mediator mainly produced by a variety of immune cells, including DCs, that exerts pleiotropic effects on immune and inflammatory responses through interaction with specific receptors expressed on the surface of target cells. Here, we review the role of IL‐6, when generated in an inflammatory context or as derived from DCs, in modulating the biologic function and activation status of DCs and emphasize the importance of searching for novel strategies to target the IL‐6/IL‐6 signaling pathway as a means to diminish the inflammatory activity of DCs in immune response or to prime the immunogenic activity of DCs in immunosuppressive conditions.
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Reviews the role of IL‐6, when generated in an inflammatory context or as derived from dendritic cells (DCs), in modulating the biological function and activation status of DCs.
At the crossroad between innate and adaptive immunity are the dendritic Cells (DCs), a "novel cell type." discovered in 1973 by Ralph Steinman. Although not entirely appreciated at first, it is clear ...that they play a critical role as specialized antigen-presenting cells and essential mediators in shaping immune reactivity and tolerance. Dendritic cells are now recognized as a heterogeneous group of cells in terms of cell-surface markers, anatomic location, and function adapted to protect against an array of pathogens and conditions. Importantly, these subsets are also unique to each species. While significant progress has been made on the identification and function of mouse DC subsets, much less is known about human cells. Here we review the fascinating biology of human skin DCs and describe tolerogenic principles that are critical in maintaining immune homeostasis and for controlling inflammation, as well as mechanisms that are fundamental to confer immunity. We surmise that these principles could be applied to DCs across organs, and could be harnessed for the treatment of various human autoimmune, inflammatory diseases, as well as cancer. Importantly, to leverage the relevance of basic research to the clinical setting, it is first necessary to determine the functional homology between mouse and human DCs. We discuss practical steps towards this aim.
While immunoglobulin A (IgA) is well known for its neutralizing and anti-inflammatory function, it is becoming increasingly clear that IgA can also induce human inflammatory responses by various ...different immune cells. Yet, little is known about the relative role of induction of inflammation by the two IgA subclasses i.e. IgA1, most prominent subclass in circulation, and IgA2, most prominent subclass in the lower intestine. Here, we set out to study the inflammatory function of IgA subclasses on different human myeloid immune cell subsets, including monocytes, and
differentiated macrophages and intestinal CD103
dendritic cells (DCs). While individual stimulation with IgA immune complexes only induced limited inflammatory responses by human immune cells, both IgA subclasses strongly amplified pro-inflammatory cytokine production upon co-stimulation with Toll-like receptor (TLR) ligands such as Pam3CSK4, PGN, and LPS. Strikingly, while IgA1 induced slightly higher or similar levels of pro-inflammatory cytokines by monocytes and macrophages, respectively, IgA2 induced substantially more inflammation than IgA1 by CD103
DCs. In addition to pro-inflammatory cytokine proteins, IgA2 also induced higher mRNA expression levels, indicating that amplification of pro-inflammatory cytokine production is at least partially regulated at the level of gene transcription. Interestingly, cytokine amplification by IgA1 was almost completely dependent on Fc alpha receptor I (FcαRI), whilst blocking this receptor only partially reduced cytokine induction by IgA2. In addition, IgA2-induced amplification of pro-inflammatory cytokines was less dependent on signaling through the kinases Syk, PI3K, and TBK1/IKKϵ. Combined, these findings indicate that IgA2 immune complexes, which are most abundantly expressed in the lower intestine, particularly promote inflammation by human CD103
intestinal DCs. This may serve an important physiological function upon infection, by enabling inflammatory responses by this otherwise tolerogenic DC subset. Since various inflammatory disorders are characterized by disturbances in IgA subclass balance, this may also play a role in the induction or exacerbation of chronic intestinal inflammation.
We report a case of severe multiple trauma treated at a hybrid operating room (hybrid OR). A 54-year-old man was brought to the emergency department with a history of a hit by a light pickup. He ...presented with hypotension, after resuscitative endovascular balloon occlusion of the aorta, trauma pan-scan CT revealed traumatic hemopneumothorax, splenic injury, and pelvic fracture. We performed damage control surgery and damage control interventional radiography for splenic injury in the hybrid OR. On day 52 he was discharged by walking. The hybrid OR could be a very effective tool for the treatment of fatal multiple trauma.
Identification of immunogenic tumor antigens that are efficiently processed and delivered by dendritic cells to prime the immune system and to induce an appropriate immune response is a research ...hotspot in the field of cancer vaccine development. High biosafety is an additional demand. Tumor-derived exosomes (TEXs) are nanosized lipid bilayer encapsulated vesicles that shuttle bioactive information to the tumor microenvironment facilitating tumor progression. However, accumulating evidence points toward the capacity of TEXs to efficiently stimulate immune responses against tumors provided they are appropriately administered. After briefly describing the function of exosomes in cancer biology and their communication with immune cells, we summarize in this review in vitro and preclinical studies eliciting the potency of TEXs in inducing effective anti-tumor responses and recently modified strategies further improving TEX-vaccination efficacy. We interpret the available data as TEXs becoming a lead in cancer vaccination based on tumor antigen-selective high immunogenicity.
Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of ...immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy. Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced cancer immunotherapy.
The phenolic nanoadjuvant (PIMS NPs) promotes significant maturation of dendritic cells thereby sensitizes tumors to PD-L1 checkpoint blockade immunotherapy. After systemic injection of PIMS NPs, the low-intensity ultrasound applied on the primary tumor site is capable of eliciting ICD to release the TAAs and DAMPs. Meanwhile, the Mn2+ can be released in situ for enhancing the activation of the cGAS-STING pathway. The combinational action of SDT-mediated ICD and activation of the cGAS-STING pathway can significantly enhance the maturation of DCs. Furthermore, the activation of antitumor T cell immune responses can realize the potential of PD-L1 checkpoint blockade immunotherapy, which efficiently inhibits the growth of distant tumors and restrains lung metastasis. Display omitted
•Sonodynamic therapy is a promising treatment that can elicit antitumor immunity by effectively killing tumor cells.•Mn2+ can promote the activation of the cGAS-STING pathway which significantly boosts the antitumor immunotherapy.•A phenolic nanoadjuvant is developed for stimulating the maturation of dendritic cells to induce the activation of T cells.•The enhanced DCs maturation can sensitize tumors to PD-L1 checkpoint blockade immunotherapy in an effective manner.
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•RNA-seq analysis found out 2293 DEGs between PSG-1 and control group.•Most of GO terms found by GO analysis were related to immune.•Cytokine, NF-κB and MAPK were among top 20 ...enriched pathways identified by KEGG.•PSG-1 induced the secretion of cytokines on DCs in Caco-2/DCs co-culture model.•NF-κB and MAPK pathways in DCs indirectly treated by PSG-1 were activated.
Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) activated the immune response of dendritic cells (DCs) by direct contacting with surface receptors. However, as a kind of macromolecule compound, PSG-1 cannot directly stimulate DCs via passing through the intestine epithelial cells. To investigate the role of PSG-1 in the interaction between the intestinal epithelium and its internal immune cells, the intestinal-like Caco-2/DCs co-culture model was established, then all transcripts of DCs with or without treatment of PSG-1 were globally screened by RNA-seq. According to the RNA-seq analysis, cytokine receptor interaction, NF-κB and MAPK signaling pathway were three important signal pathways annotate to the environmental information processing. Moreover, cytokine and related proteins expression were in DCs indirectly stimulated by PSG-1 were raised. These above findings indicated that PSG-1 indirectly affected the immune function of DCs in intestinal-like Caco-2/DCs co-culture model, in which NF-κB and MAPK pathway played essential roles.
Background Atopic dermatitis (AD) and psoriasis represent contrasting poles of the TH 1 versus TH 2 paradigm. Both diseases have been associated with increased numbers of dendritic cells (DCs) in the ...skin, but the similarities and differences in DC populations need to be established. Objective We aimed to characterize the specific DC subsets, as well as chemokine and cytokine environment in chronic AD compared with psoriasis. Methods Skin biopsies were obtained from patients with acute exacerbation of chronic AD (n = 18), psoriasis (n = 15), and healthy volunteers (n = 15) for microarray analysis, RT-PCR, immunohistochemistry, and double-label immunofluorescence. Results Myeloid DCs upregulate CCL17 and CCL18 in AD, as opposed to TNF-α and inducible nitric oxide synthase (iNOS) in psoriasis. In our study, we identified cells phenotypically identical to the inflammatory dendritic epidermal cells in the dermis in both diseases, although to a lesser extent in psoriasis. We found substantially higher numbers of dermal CCL22 producing plasmacytoid DCs in AD. The thymic stromal lymphopoietin receptor showed significantly higher expression in AD, whereas the thymic stromal lymphopoietin ligand was upregulated more in psoriasis. Conclusion There are major differences in myeloid and plasmacytoid subsets of cutaneous DCs and the chemokine/cytokine environment between AD and psoriasis. Distinct subsets within the CD11c+ population may influence polarization through the production of regulatory mediators, including iNOS, TNF, CCL17, and CCL18. Plasmacytoid DCs may also influence TH 2 polarization, having a more important role in AD than previously appreciated. Clinical implications Dermal inflammatory dendritic cells in AD and TNF and iNOS–producing DCs in psoriasis, and/or their regulatory products, may be potential targets for future therapeutic interventions.
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