scholarly journals NCoR1 and SMRT Fine-Tune Inflammatory Versus Tolerogenic Balance in Dendritic Cells By Differentially Regulating STAT3 Signaling

2022 ◽  
Author(s):  
Atimukta Jha ◽  
Abdul Ahad ◽  
Gyan Prakash Mishra ◽  
Kaushik Sen ◽  
Shuchi Smita ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dendritic Cells ◽  
Tumor Burden ◽  
Differential Regulation ◽  
Comparative Genomic ◽  
Cell Frequency ◽  
Stat3 Signaling ◽  
Immune Pathology ◽  
Fine Tune

Abstract Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by down-regulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.

scholarly journals NCoR1 and SMRT fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling

2021 ◽  
Author(s):  
A. Jha ◽  
A. Ahad ◽  
G. P. Mishra ◽  
K. Sen ◽  
S. Smita ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Tumor Burden ◽  
Differential Regulation ◽  
Comparative Genomic Analysis ◽  
Comparative Genomic ◽  
Cell Frequency ◽  
Stat3 Signaling ◽  
Immune Pathology ◽  
Fine Tune

AbstractDendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+and CD8+T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion repressed mTOR-STAT3-IL10 signaling in cDC1 by down-regulating NR4A1. Besides, NFkBIA and SOCS3 were down-regulated in SMRT knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+T-cell frequency, respectively. We also depicted decreasedSmrtexpression in Rheumatoid Arthritis, a Th1/Th17 disease.

scholarly journals Novel role of lncRNA CHRF in cisplatin resistance of ovarian cancer is mediated by miR-10b induced EMT and STAT3 signaling

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wen-Xi Tan ◽  
Ge Sun ◽  
Meng-Yuan Shangguan ◽  
Zhi Gui ◽  
Yang Bao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cisplatin Resistance ◽  
Gynecological Cancer ◽  
Acquired Resistance ◽  
Tumor Burden ◽  
Human Patient ◽  
Mesenchymal Transition ◽  
Stat3 Signaling

Abstract Ovarian Cancer (OC) is a highly lethal gynecological cancer which often progresses through acquired resistance against the administered therapy. Cisplatin is a common therapeutic for the treatment of OC patients and therefore it is critical to understand the mechanisms of resistance against this drug. We studied a paired cell line consisting of parental and cisplatin resistant (CR) derivative ES2 OC cells, and found a number of dysregulated lncRNAs, with CHRF being the most significantly upregulated lncRNA in CR ES2 cells. The findings corroborated in human patient samples and CHRF was significantly elevated in OC patients with resistant disease. CHRF was also found to be elevated in patients with liver metastasis. miR-10b was found to be mechanistically involved in CHRF mediated cisplatin resistance. It induced resistance in not only ES2 but also OVCAR and SKOV3 OC cells. Induction of epithelial-to-mesenchymal-transition (EMT) and activation of STAT3 signaling were determined to be the mechanisms underlying the CHRF-miR-10b axis-mediated cisplatin resistance. Down-regulation of CHRF reversed EMT, STAT3 activation and the resulting cisplatin resistance, which could be attenuated by miR-10b. The results were also validated in an in vivo cisplatin resistance model wherein CR cells were associated with increased tumor burden, CHRF downregulation associated with decreased tumor burden and miR-10b again attenuated the CHRF downregulation effects. Our results support a novel role of lncRNA CHRF in cisplatin resistance of OC and establish CHRF-miR-10b signaling as a putative therapeutic target for sensitizing resistant OC cells.

The role of prostaglandin E2 receptor signaling of dendritic cells in rheumatoid arthritis

2014 ◽  
Vol 23 (1) ◽  
pp. 163-169 ◽  
Author(s):  
Xiao-Yi Jia ◽  
Yan Chang ◽  
Xiao-Jing Sun ◽  
Xing Dai ◽  
Wei Wei
Keyword(s):  
Rheumatoid Arthritis ◽  
Dendritic Cells ◽  
Prostaglandin E2 ◽  
Receptor Signaling ◽  
Prostaglandin E2 Receptor

Role of Dendritic Cells in the Rheumatic Diseases Pathogenesis: Review

2021 ◽  
Vol 76 (4) ◽  
pp. 394-401
Author(s):  
Yuliya D. Kurochkina ◽  
Maxim A. Korolev
Keyword(s):  
Rheumatoid Arthritis ◽  
Dendritic Cells ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Functional Features ◽  
Antigen Presenting ◽  
Methods Of Treatment ◽  
Existing Data

Dendritic cells (DCs) are professional antigen presenting cells that can as stimulate immune response as suppress immune inflamma tion. Recently the role of DCs in the pathogenesis of autoimmune diseases and the possibility of their application as diagnostic markers and methods of treatment has been studied more and more. It was shown that subpopulations DCs play different role in pathogenesis various autoimmune diseases. Thus, pathogenesis of rheumatoid arthritis and ankylosing spondylitis is associated with activity of myeloid DCs and their possibility to present arthritogenic peptides to T-cells. While plasmocytoid DCs are more important in pathogenesis systemic lupus erythematosus and systemic sclerosis. The review presents the results of the latest registered clinical trials about applications DCs in different autoimmune diseases as well as current ideas about functional features DCs during autoimmune diseases. The existing data confirm their possible use as well as the safety of DC in treatment.

scholarly journals Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopamine in the pathogenesis of Rheumatoid Arthritis

2009 ◽  
Vol 32 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Kazuhisa NAKANO ◽  
Sho MATSUSHITA ◽  
Kazuyoshi SAITO ◽  
Kunihiro YAMAOKA ◽  
Yoshiya TANAKA
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Modulator

scholarly journals Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis

2009 ◽  
Vol 69 (3) ◽  
pp. 618-623 ◽  
Author(s):  
Lode Melis ◽  
Bernard Vandooren ◽  
Elli Kruithof ◽  
Peggy Jacques ◽  
Martine De Vos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Th17 Cells ◽  
Differential Regulation ◽  
Effector T Cell ◽  
Inflammatory Conditions ◽  
Gene Coding ◽  
Local Parameters ◽  
Th17 Cytokine

ObjectivesTh17 cells are an effector T-cell population that plays a role in chronic inflammatory conditions and is dependent on IL-23 for their survival and expansion. More recently, a genetic association was discovered between polymorphisms in the gene coding for the IL-23 receptor and spondyloarthritis. This study aimed to evaluate the role of Th17-associated cytokines in spondyloarthritis pathogenesis by measuring their levels in the joints and circulation as well as correlating them with disease activity parameters.MethodsPaired synovial fluid (SF), serum and synovial biopsies were obtained from 30 non-PsA (psoriatic arthritis) spondyloarthritis, 22 PsA and 22 rheumatoid arthritis (RA) patients. IL-17, IL-23 and CCL20 were measured by ELISA in the SF and serum of patients and correlated with systemic and local parameters of disease activity.ResultsConcentrations of CCL20, a major Th17-attracting chemokine, tended to be higher in the joints of RA than in spondyloarthritis patients. Interestingly, levels of CCL20 were markedly higher in SF as opposed to serum. In addition, there was a remarkable association between the expression of the Th17 cytokine system and the presence of intimal lining layer hyperplasia in RA. Also in the serum, there was a tendency for higher IL-23 levels in RA, which correlated strongly with disease activity parameters.ConclusionsTh17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.

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