scholarly journals T-Bet Deficiency Attenuates Bile Duct Injury in Experimental Biliary Atresia

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3461
Author(s):  
Sujit K. Mohanty ◽  
Bryan Donnelly ◽  
Haley Temple ◽  
Alexander Bondoc ◽  
Monica McNeal ◽  
...  
Keyword(s):  
Biliary Atresia ◽  
Mononuclear Cells ◽  
Wild Type ◽  
T Helper ◽  
T Helper 1 ◽  
Targeted Deletion ◽  
Extrahepatic Bile Ducts ◽  
Inflammatory Profile ◽  
End Stage ◽  
Overall Mortality

Biliary atresia (BA) is an obstructive neonatal cholangiopathy leading to liver cirrhosis and end stage liver disease. A Kasai portoenterostomy may restore biliary drainage, but most patients ultimately require liver transplantation for survival. At diagnosis, immune cells within the liver of patients with BA demonstrate a T-helper 1 (Th1) inflammatory profile similar to rhesus rotavirus (RRV)-infected mice livers developing BA. The transcription factor Tbx21 (T-bet) is essential for induction of a Th1 immune response in both the adaptive and innate immune system. Here we used animals with targeted deletion of the T-bet gene to determine its role in the progression of BA. Infection of newborn T-bet knockout (KO) pups with RRV resulted in a decreased Th1 inflammatory chemokine/cytokine profile when compared to infected wild-type mice. Analysis of the mononuclear cells profile from T-bet KO mice revealed both a significant decrease in the total number of CD3, CD4, and CD8 T cells and their effector molecules granzyme A, perforin, and FasL. Even though the percentage of T-bet KO mice displaying symptoms of an obstructive cholangiopathy and overall mortality rate was not different compared to wild-type mice, the extrahepatic bile ducts of T-bet KO mice remained patent.

scholarly journals Cytokine Signature in End-Stage Renal Disease Patients on Hemodialysis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Danyelle Romana Alves Rios ◽  
Melina Barros Pinheiro ◽  
Wander Valadares de Oliveira Junior ◽  
Karina Braga Gomes ◽  
Andréa Teixeira Carvalho ◽  
...  
Keyword(s):  
Renal Disease ◽  
Vascular Access ◽  
The Body ◽  
T Helper ◽  
T Helper 1 ◽  
Group I ◽  
Group Ii ◽  
Inflammatory Profile ◽  
Stage Renal Disease ◽  
End Stage

Hemodialysis is a modality of blood filtration in which accumulated toxins and water are removed from the body. This treatment is indicated for patients at the end stage of renal disease. Vascular access complications are responsible for 20–25% of all hospitalizations in dialyzed patients. The occurrence of thrombosis in the vascular access is a serious problem that may severely compromise or even make the hemodialysis impossible, which is vital for the patient. The aim of this study was to investigate inflammatory profile in patients undergoing hemodialysis as well as the association between these alterations and vascular access thrombosis. A total of 195 patients undergoing hemodialysis have been evaluated; of which, 149 patients had not experienced vascular access thrombosis (group I) and 46 patients had previously presented this complication (group II). Plasma levels of cytokines including interleukin (IL-) 2, IL-4, IL-5, IL-10, TNF-α, and IFN-γwere measured by cytometric bead array. Our results showed that patients with previous thrombotic events (group II) had higher levels of the IL-2, IL-4, IL-5, and IFN-γwhen compared to those in group I. Furthermore, a different cytokine signature was detected in dialyzed patients according to previous occurrences or not of thrombotic events, suggesting that elevated levels of T-helper 1 and T-helper 2 cytokines might, at least in part, contribute to this complication.

Abstract 425: Lycopene Modulates T Lymphocyte Function by Modulating Th1 Responses and Treg Lymphocyte Population

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Lynsey M Mills ◽  
Heather Wilson ◽  
Frank Thies
Keyword(s):  
T Lymphocyte ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Lymphocyte Function ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear ◽  
Lymphocyte Activity ◽  
Ifn Γ

Increased lycopene intake might have cardiovascular benefits, potentially through anti-inflammatory mechanisms. We recently showed that lycopene can influence lymphocyte activity by modulating processes involved in early cellular activation. T lymphocytes comprise different subsets, T cytotoxic, T helper 1 (Th1), T helper 2 (Th2) and T regulatory cells (Treg). We aimed to determine whether lycopene could specifically modulate T-cell subsets function and activity. Peripheral blood mononuclear cells from 11 healthy adults were cultured for 18hr to 60h in the presence of lycopene-enriched liposomes (0-1.18μg lycopene/ml) with or without mitogens. The secretion of cytokines representative of Th1,Th2 and Treg activities were measured by ELISA (IL-2, IL-1β, IL-10, IFN-γ and TGF-β) or cytometric bead array (IL-4, IL-10, IL17 and IFN-γ). The population profile of Tc (CD3+/CD8+), Th (CD3+/CD4+), Treg (CD4+/CD25+), and the Treg subsets nTreg (CD4+/CD25+/FoxP3+) and iTreg (CD4+/CD25+/IL-10+) was determined by flow cytometry. After 18h incubation, IL-2 concentration in the medium was significantly reduced (-29%, p=0.001) in the presence of lycopene (1.18μg/mL). Similar effects were observed after 36h and 60h culture for IFN-γ (-23%, p=0.015), Il-10 (-30%, p=0.023), IL-17 (-30%, p=0.019) but not IL-4 or TGF-β. The proportion of Treg cell was also significantly increased by 36% (p=0.001) in the presence of lycopene (1.18μg/mL) compared with non-treated activated cells. Furthermore, the proportions of iTreg cells were significantly increased by after incubation with lycopene while the proportion of nTreg cells decreased (-20.5 %, p=0.049). We conclude that increased lycopene intake may be beneficial against atherogenesis by modulating T lymphocyte function, particularly in relation toTh1 and Treg.

Immunopotent Polysaccharides of Different Sources Selectively Activate Human Dendritic Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3873-3873
Author(s):  
Godfrey ChiFung Chan ◽  
W.K. Chan ◽  
H.K. Law ◽  
Z.B. Lin ◽  
Y.L. Lau
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
T Helper ◽  
T Helper 1 ◽  
Xtt Assay ◽  
Peripheral Blood Mononuclear ◽  
Human Dendritic Cells

Abstract Background: Purified polysaccharides extracted from plants and fungi have been shown to induce immune responses in-vivo and vitro over the past decade. Currently, most of these polysaccharides are found to be glucan but with different branch structure and sizes. Their relative potency and effect on human immune cells remains unknown. This study aims to compare their relative effect on human dendritic cell, the most potent antigen presenting cell. Materials & Methods: We selected 2 prototypes of purified polysaccharides extracted from: 1) Ganoderma lucidum (GL, Lingzhi, Reishi) mycelium, a widely used herb with long and branching β (1® 3), (1® 6) glucan structure (provided by Prof. Lin ZB, Beijing) and 2) Barley with shorter and different branching β (1® 3), (1® 4) structure (provided by Prof. Cheung VNK, NY). Their characteristics and chemical properties had been reported previously. Human peripheral blood mononuclear cells (PBMCs) proliferation was studied by XTT assay. Human dendritic cells (DCs) were derived from monocytes and maturation of DCs were determined by: a) immunophenotypic shift using flow cytometer; 2) dextran endocytosis assay and 3) mixed lymphocytes reaction. Cytokine secretions were determined by ELISA test. Comparisons between means were by nonparametric Student’s t test (2-tailed). Results: We found that purified polysaccharides from GL but not barley could induce PBMCs proliferation and maturation of DCs. GL polysaccharides could enhance phenotypic and functional maturation of DCs with significant IL-12 and IL-10 production. DCs were relatively inert to Barley glucans stimulation. However, both polysaccharides did not polarize T cells into the direction of T helper 1, T helper 2 or regulatory T cells. Conclusions: Our study shown that purified polysaccharides extracted from plants and fungi have different effect on human DCs and their potency and effects are probably affected by their respective sources and structures.

Evaluation of the potential anti-allergic effects of heat-inactivated Lactobacillus paracasei V0151 in vitro, ex vivo, and in vivo

2015 ◽  
Vol 6 (5) ◽  
pp. 697-705 ◽  
Author(s):  
Y.W. Liu ◽  
T.Y. Fu ◽  
W.S. Peng ◽  
Y.H. Chen ◽  
Y.M. Cao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Lactobacillus Paracasei ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear

The efficacy of Lactobacillus paracasei V0151 (V0151), isolated from the faeces of a child, to modulate immune responses was investigated. In RAW 264.7 cells expressing an inducible nitric oxide synthase (iNOS)-directed luciferase gene, heat-inactivated V0151 stimulated iNOS expression followed by nitric oxide production. V0151 significantly elevated interferon gamma, interleukin (IL)-10, tumour necrosis factor alpha, and IL-1β production in human peripheral blood mononuclear cells. In splenocytes isolated from ovalbumin (OVA)-sensitised BALB/c mice treated with OVA and V0151 at different bacterium-to-cell ratios (1:1, 10:1, and 20:1) for 96 h, IL-2, IL-4, IL-5, and IL-13 production was dose-dependently downregulated, whereas IL-12 was dose-dependently upregulated. Collectively, our findings indicate that V0151 might regulate pro-inflammatory factors in macrophages and splenocytes. Furthermore, the T helper 1/T helper 2 (Th1/Th2) balance was also skewed toward Th1 dominance through the elevation of Th1 cytokine production.

CD4+/CD8+ macrophages infiltrating at inflammatory sites: a population of monocytes/macrophages with a cytotoxic phenotype

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2004-2012 ◽  
Author(s):  
Tomohisa Baba ◽  
Akihiro Ishizu ◽  
Sari Iwasaki ◽  
Akira Suzuki ◽  
Utano Tomaru ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Mononuclear Cells ◽  
Type I ◽  
Wild Type ◽  
T Helper 1 ◽  
Double Positive ◽  
Peripheral Blood Mononuclear ◽  
Cell Leukemia Virus Type ◽  
Gm Csf ◽  
Human T Cell

We found a population of nonlymphoid cells expressing both CD4 and CD8 in peripheral blood mononuclear cells (PBMCs) of human T-cell leukemia virus type-I pX transgenic rats with autoimmune diseases. These cells, which showed a monocytic phenotype, were also found in wild-type rats, and their number increased by adjuvant-assisted immunization. GM-CSF increased the number of these double-positive (DP) monocytes in PBMCs. Consistent with the idea that DP monocytes differentiate into DP macrophages at sites of inflammation, we found infiltration of DP macrophages at the site of myosin-induced myocarditis in wild-type rats; these cells exhibited a T-helper 1 (Th1)-type cytokine/chemokine profile and expressed high levels of Fas ligand, perforin, granzyme B, and NKR-P2 (rat orthologue of human NKG2D). Adoptive transfer of GFP-positive spleen cells confirmed hematogenous origin of DP macrophages. DP monocytes had a cytotoxic phenotype similar to DP macrophages, indicating that this phenotypic specialization occurred before entry into a tissue. In line with this, DP monocytes killed tumor cells in vitro. Combined evidence indicates that certain inflammatory stimuli that induce GM-CSF trigger the expansion of a population of DP monocytes with a cytotoxic phenotype and that these cells differentiate into macrophages at inflammatory sites. Interestingly, human PBMCs also contain DP monocytes.

scholarly journals P-Selectin Glycoprotein Ligand 1 (Psgl-1) Is a Physiological Ligand for E-Selectin in Mediating T Helper 1 Lymphocyte Migration

2000 ◽  
Vol 192 (11) ◽  
pp. 1669-1676 ◽  
Author(s):  
Takako Hirata ◽  
Glenn Merrill-Skoloff ◽  
Melissa Aab ◽  
Jing Yang ◽  
Barbara C. Furie ◽  
...  
Keyword(s):  
Contact Hypersensitivity ◽  
Th1 Cells ◽  
Wild Type ◽  
T Helper ◽  
Lymphocyte Migration ◽  
T Helper 1 ◽  
Deficient Mice

P-selectin glycoprotein ligand 1 (PSGL-1) is a sialomucin expressed on leukocytes that mediates neutrophil rolling on the vascular endothelium. Here, the role of PSGL-1 in mediating lymphocyte migration was studied using mice lacking PSGL-1. In a contact hypersensitivity model, the infiltration of CD4+ T lymphocytes into the inflamed skin was reduced in PSGL-1–deficient mice. In vitro–generated T helper (Th)1 cells from PSGL-1–deficient mice did not bind to P-selectin and migrated less efficiently into the inflamed skin than wild-type Th1 cells. To assess the role of PSGL-1 in P- or E-selectin–mediated migration of Th1 cells, the cells were injected into E- or P-selectin–deficient mice. PSGL-1–deficient Th1 cells did not migrate into the inflamed skin of E-selectin–deficient mice, indicating that PSGL-1 on Th1 cells is the sole ligand for P-selectin in vivo. In contrast, PSGL-1–deficient Th1 cells migrated into the inflamed skin of P-selectin–deficient mice, although less efficiently than wild-type Th1 cells. This E-selectin–mediated migration of PSGL-1–deficient or wild-type Th1 cells was not altered by injecting a blocking antibody to L-selectin. These data provide evidence that PSGL-1 on Th1 cells functions as one of the E-selectin ligands in vivo.

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