scholarly journals Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pedro Rodríguez-Jiménez ◽  
Lola Fernández-Messina ◽  
María C. Ovejero-Benito ◽  
Pablo Chicharro ◽  
Paula Vera-Tomé ◽  
...  
Keyword(s):  
T Cells ◽  
Dna Repair ◽  
Dendritic Cells ◽  
Growth Arrest ◽  
Lesional Skin ◽  
Psoriatic Disease ◽  
Peripheral T Cells ◽  
Demethylase Activity ◽  
Circulating T Cells ◽  
Lower Expression

AbstractThe interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.

scholarly journals Growth Arrest and DNA Damage-Ind­ucible Proteins (GADD45) in Psoriasis

2020 ◽  
Author(s):  
Pedro Rodríguez-Jiménez ◽  
Lola Fernández-Messina ◽  
María Ovejero-Benito ◽  
Pablo Chicharro ◽  
Alicia Vara ◽  
...  
Keyword(s):  
T Cells ◽  
Dna Repair ◽  
Dendritic Cells ◽  
Growth Arrest ◽  
Lesional Skin ◽  
Psoriatic Disease ◽  
Inflammatory Signals ◽  
Peripheral T Cells ◽  
Circulating T Cells ◽  
Lower Expression

Abstract The interplay between T cells, dendritic cells and keratinocytes is crucial in the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in many cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation by mediating demethylation. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells from psoriasis patients and their regulation by inflammatory signals. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. Expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to non-lesional skin and controls. Furthermore, hypermethylation correlated with lower levels of both GADD45a and UCHL1 in lesional skin. The demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.

scholarly journals A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis.

1996 ◽  
Vol 183 (4) ◽  
pp. 1789-1796 ◽  
Author(s):  
G Süss ◽  
K Shortman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Activated T Cells ◽  
T Cell Apoptosis ◽  
Peripheral T Cells ◽  
Surface Staining ◽  
Induced Apoptosis ◽  
Antigen Presenting

Dendritic cells (DC), the most efficient antigen-presenting cells, are well equipped for activation of naive CD4+ T cells by their expression of high levels of major histocompatibility complex and costimulator molecules. We now demonstrate that some DC are equally well equipped for killing these same T cells. Murine splenic DC consist of both conventional CD8alpha- DC and a major population of CD8alpha+ DC. Whereas CD8- DC induce a vigorous proliferative response in CD4 T cells, CD8+ DC induce a lesser response that is associated with marked T cell apoptosis. By using various mixtures of T cells and DC from Fas-mutant lpr/lpr mice and Fas-ligand (FasL) mutant gld/gld mice, we show this death is due to interaction of Fas on activated T cells with FasL on CD8+ DC. Furthermore, we show by direct surface staining that CD8+ DC, but not CD8- DC, express FasL at high levels. These findings indicate that FasL+ CD8+ DC are a specialized subgroup of DC with a role in the regulation of the response of primary peripheral T cells.

scholarly journals Dietary grape seed proanthocyanidins inactivate regulatory T cells by promoting NER-dependent DNA repair in dendritic cells in UVB-exposed skin

Oncotarget ◽  
2017 ◽  
Vol 8 (30) ◽  
pp. 49625-49636 ◽  
Author(s):  
Mudit Vaid ◽  
Ram Prasad ◽  
Tripti Singh ◽  
Santosh K. Katiyar
Keyword(s):  
T Cells ◽  
Dna Repair ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Grape Seed ◽  
Grape Seed Proanthocyanidins ◽  
Exposed Skin

Comparison of Gene Expression between T Cells from CLL Patients, Myeloma Patients and Healthy Individuals.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4674-4674
Author(s):  
Aniruddha Choudhury ◽  
Anders Osterborg ◽  
Kaveh Mashayakhi ◽  
Ali Mosfegh ◽  
Shahryar Kiaii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
T Cells ◽  
Cell Clone ◽  
Differential Expression Analysis ◽  
Lymphocytic Leukemia ◽  
Healthy Individuals ◽  
Peripheral T Cells ◽  
Leukemic Clone ◽  
Circulating T Cells

Abstract A unique feature of chronic lymphocytic leukemia is the expansion in absolute numbers of circulating T cells, accompanying the increase in the leukemic B cell clone. T cells of CLL patients may have a role in contributing to the microenvironment that favors the survival and progression of the malignant clone. We have looked at the gene profile of highly purified peripheral T cells from indolent CLL patients using Affymetrix global gene arrays and compared them with purified T cells from multiple myeloma patients as well as healthy individuals. T cells from five indolent, treatment-naïve CLL patients were examined for gene expression by Affymetrix-based microarray alongside T cells from 5 stage I, multiple myeloma patients and 5 age-matched healthy volunteers. Differential expression analysis revealed that 356 genes were differentially expressed by T cells from CLL patients. Based on a two-fold or greater difference, 107 genes were specifically upregulated and 247 genes were noted to be specifically downregulated in T cells of CLL patients. The highest level of upregulation was noted for the chemokines XCL1, XCL2, and the cytokine IFN-g. CCL4 and CCL5 were two other important chemokines that also were found to be specifically upregulated in T cells of B-CLL patients as well as KLF6 and TRAF1. The findings of the microarray analysis was further confirmed using quantitative real-time PCR and immunoblotting with specific antibodies. using T cells from an additional 14 CLL, 6 multiple myeloma and 10 healthy individuals. Our results indicate that T cells from B CLL patients may express a variety of genes that contribute to the creation of a microenvironment that sustains the survival of the leukemic clone and may produce soluble factors that inhibit apoptosis and facilitate proliferation of the leukemic B cells.

scholarly journals Primary Peripheral T Cells Become Susceptible to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Mediated Apoptosis in Vitro upon Activation and in the Presence of Dendritic Cells

2008 ◽  
Vol 73 (6) ◽  
pp. 1722-1735 ◽  
Author(s):  
Narendra P. Singh ◽  
Mitzi Nagarkatti ◽  
Prakash Nagarkatti
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Peripheral T Cells ◽  
Tetrachlorodibenzo P Dioxin

Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 156-156
Author(s):  
Khursheed Anwer ◽  
Junko Matsuzaki ◽  
Wiam Bshara ◽  
Amit Lugade ◽  
Angela Omilian ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Intraperitoneal Administration ◽  
Cell Populations ◽  
Newly Diagnosed ◽  
Myeloid Dendritic Cells ◽  
Peritoneal Cancer ◽  
Circulating T Cells

156 Background: The translational component of a Phase I study of weekly intraperitoneal GEN-1, an IL-12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, in combination with dose-dense weekly taxane (T) and carboplatinum (C) every 3 weeks in newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) patients undergoing neoadjuvant therapy (NAC). Our hypothesis is that the GEN-1 plus NAC treatment will reprogram the tumor immune microenvironment towards a potent antitumor immune response. Methods: Patients received GEN-1 at escalating dose levels from 36 mg/m2, 47 mg/m2, 61 mg/m2, to 79 mg/m2weekly for 8 treatments with concurrent T/C. Tumor samples collected at time of diagnostic laparoscopy and interval debulking (IDB). Blood and peritoneal ascites were collected before and after treatment. The immunological analysis included frequency of immune cell populations and cytokine levels in tumor, blood, and peritoneal ascites and cell-specific mRNA expression profile. Results: The preliminary results obtained from first two cohorts show that GEN-1 may be enhancing post-treatment changes in immune cell populations including an increase in cytotoxic CD8+ T-cells and decrease in immunosuppressive FoxP3+ T-reg cells in tumor at IDB. The CD8:Foxp3 ratio appeared to be skewing beneficially towards more cytotoxic T lymphocyte and away from suppressive cells in most patients. The analysis of circulating immune cells 21 days after first GEN-1 treatment showed a decrease in circulating CD123+ plasmacytoid dendritic cells, but no change in CD11c+ myeloid dendritic cells. There were no major changes in the frequency of circulating T-cells. Additional analyses from this study are in progress. Conclusions: Based on preliminary analyses of cohorts 1 & 2 samples analyzed, the treatment of EOC patients with GEN-1 and NAC has resulted in favorable immunological responses. Updated results to be presented at meeting. Clinical trial information: NCT02480374.

scholarly journals Immunological Unresponsiveness Characterized by Increased Expression of CD5 on Peripheral T Cells Induced by Dendritic Cells In Vivo

Immunity ◽  
2004 ◽  
Vol 20 (6) ◽  
pp. 695-705 ◽  
Author(s):  
Daniel Hawiger ◽  
Revati F Masilamani ◽  
Estelle Bettelli ◽  
Vijay K Kuchroo ◽  
Michel C Nussenzweig
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Peripheral T Cells

scholarly journals Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells

2013 ◽  
Vol 85 (8) ◽  
pp. 1066-1076 ◽  
Author(s):  
Mudit Vaid ◽  
Ram Prasad ◽  
Tripti Singh ◽  
Craig A. Elmets ◽  
Hui Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Dna Repair ◽  
Dendritic Cells ◽  
Ultraviolet Radiation ◽  
Immune Suppression ◽  
Effector T Cells ◽  
Radiation Induced ◽  
Stimulation Of
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