scholarly journals Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone Matings

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mengzhou He ◽  
Ming Jiang ◽  
Yuan Zhou ◽  
Fanfan Li ◽  
Meitao Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Pregnancy Loss ◽  
Mononuclear Cells ◽  
Recurrent Miscarriage ◽  
Normal Pregnancy ◽  
Immune Deviation ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Th2 Immunity ◽  
Maternal Fetal Interface

Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy.

Cytokine production by peripheral blood mononuclear cells in recurrent miscarriage

Cytokine ◽  
2004 ◽  
Vol 28 (2) ◽  
pp. 83-86 ◽  
Author(s):  
Hadinedoushan Hossein ◽  
Mirahmadian Mahroo ◽  
Aflatounian Abbas ◽  
Akbari Firouzeh ◽  
Hatmi Nadia
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Recurrent Miscarriage ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals The Combination of Patient Profiling and Preclinical Studies in a Mouse Model Based on NOD/Scid IL2Rγ null Mice Reconstituted With Peripheral Blood Mononuclear Cells From Patients With Ulcerative Colitis May Lead to Stratification of Patients for Treatment With Adalimumab

2019 ◽  
Vol 26 (4) ◽  
pp. 557-569
Author(s):  
Henrika Jodeleit ◽  
Janina Caesar ◽  
Christina Villarroel Aguilera ◽  
Sebastian Sterz ◽  
Lesca Holdt ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mouse Model ◽  
Hierarchical Clustering ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Nsg Mice ◽  
Immunological Phenotype ◽  
Blood Mononuclear Cells

Abstract Background To date, responsiveness to tumor necrosis factor alpha inhibitors in ulcerative colitis (UC) patients is not predictable. This is partially due to a lack of understanding of the underlying inflammatory processes. The aim of this study was to identify immunological subgroups of patients with UC and to test responsiveness to adalimumab in these subgroups in the mouse model of ulcerative colitis (UC), which is based on NOD/scid IL-2Rγ null (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMCs; NSG-UC). Methods The immunological profiles of 40 UC patients and 16 non-UC donors were determined by flow cytometric analysis of PBMCs in a snapshot and longitudinal study and analyzed by principal component, orthogonal partial least square discrimination (oPLS-DA), and hierarchical clustering analysis. NSG mice were reconstituted 5 times at consecutive time points with PBMCs from a single donor and were analyzed for frequencies of human leukocytes and histological phenotype. The response to adalimumab of 2 identified subgroups was tested in the NSG-UC model. We used the clinical, colon, and histological score, serum levels of glutamic and aspartic acid, and IL-6 and IL-1ß. Response was analyzed by oPLS-DA. Results Analysis revealed a distinction between UC and non-UC donors. Hierarchical clustering identified 2 major subgroups in UC patients. Group I was characterized by TH17 and M1 monocytes, group II by TH2/TH1, and switched B cells. These subgroups reflect the dynamics of inflammation as patients. NSG-UC mice achieved an immunological phenotype reflecting the patient’s immunological phenotype. oPLS-DA revealed that NSG-UC mice reconstituted with PBMCs from group II responded better to adalimumab. Conclusions The combination of profiling and testing of therapeutics in the NSG-UC model may lead to individualized and phase-dependent therapies.

scholarly journals miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Guoping Zheng ◽  
Guanguan Qiu ◽  
Menghua Ge ◽  
Jianbiao Meng ◽  
Geng Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Disease Severity ◽  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory

Background. Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differentiate between sepsis and infection based on Sepsis-3 definition. Methods. A total of 62 patients (41 with sepsis and 21 with infection suffering from pneumonia but without sepsis) and 20 healthy controls were enrolled into the study. PBMC at admission were examined for a panel of 4 miRNAs (miR-10a, miR-17, miR-27a, and miR-125b), which have been documented to participate in inflammatory response in immune cells, via qRT-PCR. Data were validated in a mouse model of sepsis induced via cecal ligation and puncture (CLP) and THP-1 monocytes. Results. miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with patients with infection and healthy controls. miR-10a levels were negatively correlated with disease severity scores as well as levels for c-reactive protein and procalcitonin. In addition, low miR-10a expression had a diagnostic value for sepsis and a prognostic value for 28-day mortality in receiving operating characteristic analysis. Compared with infection patients and healthy controls, PBMC from sepsis patients also had higher levels of mitogen-activated kinase kinase kinase 7 (MAP3K7), a known target protein of miR-10a and an activator of the NF-κB pathway. In the mouse model of CLP-induced sepsis, miR-10a levels in PBMC were significantly decreased as early as 8 h after CLP. Overexpression of miR-10a in THP-1 cells significantly reduced the expression of MAP3K7 and proinflammatory cytokines including IL-6, TNF-α, and MCP-1. Conclusions. PBMC miR-10a levels are decreased in sepsis and negatively correlated with the disease severity. Levels of miR-10a could distinguish between sepsis and infection and predict 28-day mortality. miR-10a plays an anti-inflammatory role in the pathogenesis of sepsis.

scholarly journals Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease

2015 ◽  
Vol 309 (11) ◽  
pp. G910-G917 ◽  
Author(s):  
Na Tian ◽  
Daniel A. Leffler ◽  
Ciaran P. Kelly ◽  
Joshua Hansen ◽  
Eric V. Marietta ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Mouse Model ◽  
Immune Responses ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Gliadin Antibodies ◽  
Blood Mononuclear Cells ◽  
Hla Dq2

Celiac disease (CD) is an inflammatory disorder triggered by ingested gluten, causing immune-mediated damage to the small-intestinal mucosa. Gluten proteins are strikingly similar in amino acid composition and sequence to proline-rich proteins (PRPs) in human saliva. On the basis of this feature and their shared destination in the gastrointestinal tract, we hypothesized that salivary PRPs may modulate gluten-mediated immune responses in CD. Parotid salivary secretions were collected from CD patients, refractory CD patients, non-CD patients with functional gastrointestinal complaints, and healthy controls. Structural similarities of PRPs with gluten were probed with anti-gliadin antibodies. Immune responses to PRPs were investigated toward CD patient-derived peripheral blood mononuclear cells and in a humanized transgenic HLA-DQ2/DQ8 mouse model for CD. Anti-gliadin antibodies weakly cross-reacted with the abundant salivary amylase but not with PRPs. Likewise, the R5 antibody, recognizing potential antigenic gluten epitopes, showed negligible reactivity to salivary proteins from all groups. Inflammatory responses in peripheral blood mononuclear cells were provoked by gliadins whereas responses to PRPs were similar to control levels, and PRPs did not compete with gliadins in immune stimulation. In vivo, PRP peptides were well tolerated and nonimmunogenic in the transgenic HLA-DQ2/DQ8 mouse model. Collectively, although structurally similar to dietary gluten, salivary PRPs were nonimmunogenic in CD patients and in a transgenic HLA-DQ2/DQ8 mouse model for CD. It is possible that salivary PRPs play a role in tolerance induction to gluten early in life. Deciphering the structural basis for the lack of immunogenicity of salivary PRPs may further our understanding of the toxicity of gluten.

scholarly journals Paeoniflorin suppresses inflammatory response in imiquimod-induced psoriasis-like mice and peripheral blood mononuclear cells (PBMCs) from psoriasis patients

2016 ◽  
Vol 94 (8) ◽  
pp. 888-894 ◽  
Author(s):  
Tao Chen ◽  
Li-xin Fu ◽  
Li-wen Zhang ◽  
Bin Yin ◽  
Pei-mei Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Psoriasis Vulgaris ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model. The effects of PF on inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris were also observed. Our results indicated that PF effectively attenuated the clinical and histopathologic changes in IMQ-induced psoriasis-like mouse model. Furthermore, PF reduced the infiltration of T cells, CD11c+DCs, and neutrophils in lesional skin. In addition, PF also significantly decreased the mRNA expression of inflammatory cytokines, such as IL-17, INF-γ, IL-6, and TNF-α, in IMQ-induced psoriasis-like mouse model and PBMCs from patients with psoriasis vulgaris. Hence, our data suggest that PF can inhibit leukocyte infiltration and decrease the expression of inflammatory cytokines such as IL-17, INF-γ, IL-6, and TNF-α. PF might be a candidate drug for the treatment of psoriasis.

scholarly journals The Induction of Circulating, ACAID-Inducing Monocytes Requires CCR2/CCL2-Dependent Migration of Circulating F4/80+ Cells into the Anterior Chamber

2010 ◽  
Vol 2 ◽  
pp. OED.S6113 ◽  
Author(s):  
Robert E Cone ◽  
Subhasis Chattopadhyay ◽  
Roshan Pais ◽  
Sourojit Bhowmick ◽  
Roshanak Sharafieh ◽  
...  
Keyword(s):  
T Cells ◽  
Anterior Chamber ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Cell Mediated Immunity ◽  
Immune Deviation ◽  
Peripheral Blood Mononuclear ◽  
Intracameral Injection ◽  
Blood Mononuclear Cells ◽  
Regulatory Phenotype

To determine the origin of peripheral blood mononuclear cells (PBMC) that activate regulatory T cells in anterior chamber-associated immune deviation (ACAID), fluorescein-labeled PBMC were intravenously injected into mice before the mice received an intracameral injection of antigen. Six-24 hr after intracameral injection, fluorescein-labeled PBMC increased in the iris. Twenty-four-48 hr labeled cells decreased in the iris and increased in the thymus and spleen. The entry of the labeled PBMC into the anterior chamber and subsequent production of PBMC that transfer ACAID required the expression of CCR2 by the PBMC and the production of the chemokine CCL2 by the recipient of the PBMC. The results suggest that the intracameral injection of antigen induces i) the infiltration of F4/80+ PBMC into the AC, ii) where these PBMC are converted to a regulatory phenotype, and iii) recirculate to activate T cells that suppress cell-mediated immunity.

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