scholarly journals Fast maturation of splenic dendritic cells upon TBI is associated with FLT3/FLT3L signaling

2021 ◽  
Author(s):  
Jin Zhang ◽  
Zhenghui Li ◽  
Akila Chandrasekar ◽  
Li Shun ◽  
Albert C. Ludolph ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Response ◽  
Cross Talk ◽  
Ethanol Intoxication ◽  
Mhc Ii ◽  
Significant Burden ◽  
Almost All ◽  
Substantial Change ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Systemic inflammatory consequences remain a significant burden after traumatic brain injury (TBI), with almost all organs affected. The spleen is connected with the brain by autonomic innervation and by soluble mediators, and the cross-talk between brain and spleen may be important to establish the systemic inflammatory response to TBI. Ethanol intoxication, the most common comorbidity of TBI, is posited to influence the peripheral inflammatory response either directly or through the brain-spleen cross-talk. Here we show that TBI causes a substantial change in transcription of genes associated with dendritic cells activation in the spleen, in particular a FLT3/FLT3L induction 3h after TBI, which was enhanced by EI. The FLT3L induction was associated with the phosphorylation of FLT3 receptor in CD11c+ dendritic cells, which enhanced the protein synthesis of a subset of mRNAs, as shown by the increase in pS6, peIF2A levels in dendritic cells. This corresponded to the upregulation of proteins associated with maturation process and immunostimulatory properties such MHC-II, LAMP1 and CD68, and of pro-inflammatory cytokines such as TNFα. Notably, EI enhanced the maturation of dendritic cells. However, whereas TBI decreases expression of the adrenergic 2b receptors on dendritic cells, EI increased it, thus augmenting the chances of cross-talk regulation of immune function by the autonomic system. In conclusion, this data indicates that TBI induces a fast maturation of the immunomodulatory functions of dendritic cells which is associated by FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.

scholarly journals The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen-jian Chen ◽  
Xiao Yu ◽  
Xin-Rong Yuan ◽  
Bang-jie Chen ◽  
Na Cai ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Autoimmune Diseases ◽  
Future Research ◽  
Dependent Manner ◽  
Receptor Complexes ◽  
Multiple Organs ◽  
Pro Inflammatory Cytokines

A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36β, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.

Glutathione-S-transferase of Trichinella spiralis regulates maturation and function of dendritic cells

Parasitology ◽  
2019 ◽  
Vol 146 (14) ◽  
pp. 1725-1732 ◽  
Author(s):  
Xuemin Jin ◽  
Yong Yang ◽  
Xiaolei Liu ◽  
Haining Shi ◽  
Xuepeng Cai ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cellular Response ◽  
Trichinella Spiralis ◽  
Detoxification Enzymes ◽  
Glutathione S Transferase ◽  
Mhc Ii ◽  
The Family ◽  
And Function ◽  
Pro Inflammatory Cytokines

AbstractImmunomodulation by molecules from Trichinella spiralis (T. spiralis) has been widely reported. Glutathione-S-transferase (GST) is a major immune-modulator of the family of detoxification enzymes. Dendritic cells (DCs) are an important target for the regulation of the immune response by T. spiralis. In this study, the recombinant GST of T. spiralis (rTs-GST) was expressed and purified. rTs-GST induced low CD40 expression and moderate CD80, CD86 and MHC-II expressions and inhibited the increase of CD40, CD80 and CD86 on DCs induced by LPS. We showed that rTs-GST decreased the LPS-induced elevated level of pro-inflammatory cytokines of DCs and enhanced the level of regulatory cytokines IL-10 and TGF-β. Furthermore, co-culture of DCs and CD4+ T cells demonstrated that rTs-GST-treated DCs suppressed the proliferation of OVA-specific CD4+ T cells and increased the population of regulatory T cells (Tregs). rTs-GST-treated DCs induced a higher level of IL-4, IL-10 and TGF-β, but inhibited the level of IFN-γ. This indicates that rTs-GST-pulsed DCs induce both Th2-type responses and Tregs. These findings contribute to the current understanding of the immunomodulation of Ts-GST on cellular response and immunomodulation of T. spiralis.

scholarly journals TLR-dependent phagosome tubulation in dendritic cells promotes phagosome cross-talk to optimize MHC-II antigen presentation

2014 ◽  
Vol 111 (43) ◽  
pp. 15508-15513 ◽  
Author(s):  
A. R. Mantegazza ◽  
A. L. Zajac ◽  
A. Twelvetrees ◽  
E. L. F. Holzbaur ◽  
S. Amigorena ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antigen Presentation ◽  
Cross Talk ◽  
Mhc Ii

scholarly journals Role of cholinergic anti-inflammatory pathway in protecting sepsis-induced acute lung injury through regulation of the dendritic cells

2021 ◽  
Author(s):  
Ruiting Li ◽  
Xuemei Hu ◽  
Huibin Chen ◽  
Yin Yuan ◽  
Huiling Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Mice Model ◽  
Pro Inflammatory Cytokines

Abstract Background The cholinergic anti-inflammatory pathway (CAP) connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR), which is localized on the surface of the cells of immune system. CAP has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells (APCs), also express the α7nAChR. They not only play an important role in immune response priming but also in participating in the pathological process of ALI. Past studies have indicated that reducing the quantity of mature conventional DCs (cDCs) and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of CAP on maturation, function and quantity of DCs and cDCs in ALI remain unclear. Objective It was hypothesized that the activation of CAP may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and cDCs. This can be considered as an important intervention strategy for treating ALI. Methods GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist was administered in sepsis-induced ALI mice model and LPS-primed bone marrow-derived dendritic cells (BMDCs). The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, cDCs, and cDCs2 (type 2 cDCs), and the release of DC-related pro-inflammatory cytokines (such as IL-6, TNF-α, IL-18 IL-1β, IL-12p40, and HMGB1) in vivo and in vitro conditions. Results The results of the present study revealed that, GTS-21 treatment regulated the maturation of DCs and the production of DC-related pro-inflammatory cytokines in vitro and in sepsis-induced ALI mice model, it reduced the quantity of CD11c+MHCII+ cDCs and CD11c+CD11b+ cDCs2 in vivo experiment. Conclusions The activation of CAP contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, cDCs, and cDCs2.

scholarly journals TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42 in HMC3 cells

2020 ◽  
Author(s):  
Rumana Akhter ◽  
Yvonne Shao ◽  
Shane Formica ◽  
Maria Khrestian ◽  
Lynn M. Bekris
Keyword(s):  
Inflammatory Response ◽  
Microglial Cell ◽  
Amyloid Β ◽  
Inflammatory Factors ◽  
Genetic Studies ◽  
Microglial Cell Line ◽  
Induced Apoptosis ◽  
The Brain ◽  
Phagocytic Response ◽  
Pro Inflammatory Cytokines

AbstractAlzheimer’s disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to Aβ in mouse brain and primary cells. These studies show that microglia are key players in the response to Aβ and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to Aβ, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to Aβ toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. Aβ42 treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to Aβ after 24 hours requires TREM2 in HMC3 cells. Also, TREM2 inhibits Aβ induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to Aβ toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis, but it may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.

scholarly journals Systemic sterile induced-co-expression of IL-12 and IL-18 drives IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain

2020 ◽  
Author(s):  
Emilia A. Gaviglio ◽  
Javier M. Peralta Ramos ◽  
Daniela S. Arroyo ◽  
Claudio Bussi ◽  
Pablo Iribarren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Peripheral Immune System ◽  
Mhc Ii ◽  
Inflammatory Monocytes ◽  
Tnf Α ◽  
Hydrodynamic Shear ◽  
Ifn Γ ◽  
The Brain ◽  
Pro Inflammatory Cytokines

ABSTRACTThe development of neuroinflammation, as well as the progression of several neurodegenerative diseases, has been associated with the activation and mobilization of the peripheral immune system due to systemic inflammation. However, the mechanism by which this occurs remains unclear. Herein, we addressed the effect of systemic, endotoxin-free induced-co-expression of IL-12 and IL-18 in the establishment of a novel cytokine-mediated model of neuroinflammation. Following peripheral hydrodynamic shear of IL-12 plus IL-18 cDNAs in C57BL/6 mice, we induced systemic and persistent level of IL-12, which in turn promoted the elevation of circulating pro-inflammatory cytokines TNF-α and IFN-γ, accompanied with splenomegaly. Moreover, even though we identified an increased gene expression of both TNF-α and IFN-γ in the brain, only TNF-α was shown to be dispensable, revealing an IFN-γ-dependent activation of microglia and the recruitment of leukocytes, particularly of highly activated inflammatory monocytes. Taken together, our results argue for a systemic cytokine-mediated establishment and development of neuroinflammation, having identified IFN-γ as a potential target for immunotherapy.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Types of refractive errors and methods for their diagnosis

2020 ◽  
pp. 30-36
Author(s):  
Olga Lemzyakova
Keyword(s):  
Optical System ◽  
Contact Lenses ◽  
Vision Impairment ◽  
Refractive Errors ◽  
Vision Correction ◽  
Light Rays ◽  
Different Types ◽  
Almost All ◽  
Degrees Of Severity ◽  
The Brain

Refraction of the eye means its ability to bend (refract) light in its own optical system. In a normal state, which is called emmetropia, light rays passing through the optical system of the eye focus on the retina, from where the impulse is transmitted to the visual cortex of the brain and is analyzed there. A person sees equally well both in the distance and near in this situation. However, very often, refractive errors develop as a result of various types of influences. Myopia, or short-sightedness, occurs when the light rays are focused in front of the retina as a result of passing through the optical system of the eye. In this case, a person will clearly distinguish close objects and have difficulties in seeing distant objects. On the opposite side is development of farsightedness (hypermetropia), in which the focusing of light rays occurs behind the retina — such a person sees distant objects clearly, but outlines of closer objects are out of focus. Near vision impairment in old age is a natural process called presbyopia, it develops due to the lens thickening. Both myopia and hypermetropia can have different degrees of severity. The variant, when different refractive errors are observed in different eyes, is called anisometropia. In the same case, if different types of refraction are observed in the same eye, it is astigmatism, and most often it is a congenital pathology. Almost all of the above mentioned refractive errors require correction with spectacles or use of contact lenses. Recently, people are increasingly resorting to the methods of surgical vision correction.

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