scholarly journals Autoregulation of Th1-mediated inflammation by twist1

2008 ◽  
Vol 205 (8) ◽  
pp. 1889-1901 ◽  
Author(s):  
Uwe Niesner ◽  
Inka Albrecht ◽  
Marko Janke ◽  
Cornelia Doebis ◽  
Christoph Loddenkemper ◽  
...  
Keyword(s):  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Delayed Type Hypersensitivity ◽  
Effector Memory ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Th Cells ◽  
Twist1 Expression ◽  
Helix Loop Helix

The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor κB (NF-κB)–dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We show that twist1 is expressed by activated T helper (Th) 1 effector memory (EM) cells. Induction of twist1 in Th cells depended on NF-κB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 was transient after T cell receptor engagement, and increased upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression was characteristic of repeatedly restimulated EM Th cells, and thus of the pathogenic memory Th cells characteristic of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohn's disease or ulcerative colitis expressed high levels of twist1. Expression of twist1 in Th1 lymphocytes limited the expression of the cytokines interferon-γ, IL-2, and tumor necrosis factor-α, and ameliorated Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis.

PKCθ-regulated signalling in health and disease

2014 ◽  
Vol 42 (6) ◽  
pp. 1484-1489 ◽  
Author(s):  
Pulak R. Nath ◽  
Noah Isakov
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
Immunological Synapse ◽  
Cell Types ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Health And Disease

Protein kinase Cθ (PKCθ) is a key enzyme in T-lymphocytes where it plays an important role in signal transduction downstream of the activated T-cell receptor (TCR) and the CD28 co-stimulatory receptor. Antigenic stimulation of T-cells triggers PKCθ translocation to the centre of the immunological synapse (IS) at the contact site between antigen-specific T-cells and antigen-presenting cells (APCs). The IS-residing PKCθ phosphorylates and activates effector molecules that transduce signals into distinct subcellular compartments and activate the transcription factors, nuclear factor κB (NF-κB), nuclear factor of activated T-cells (NFAT) and activating protein 1 (AP-1), which are essential for the induction of T-cell-mediated responses. Besides its major biological role in T-cells, PKCθ is expressed in several additional cell types and is involved in a variety of distinct physiological and pathological phenomena. For example, PKCθ is expressed at high levels in platelets where it regulates signal transduction from distinct surface receptors, and is required for optimal platelet activation and aggregation, as well as haemostasis. In addition, PKCθ is involved in physiological processes regulating insulin resistance and susceptibility to obesity, and is expressed at high levels in gastrointestinal stromal tumours (GISTs), although the functional importance of PKCθ in these processes and cell types is not fully clear. The present article briefly reviews selected topics relevant to the biological roles of PKCθ in health and disease.

Complement C1q production by osteoclasts and its regulation of osteoclast development

2012 ◽  
Vol 447 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Boon Heng Dennis Teo ◽  
Yuri V. Bobryshev ◽  
Boon King Teh ◽  
Siew Heng Wong ◽  
Jinhua Lu
Keyword(s):  
Lupus Erythematosus ◽  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Detection Methods ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Blood Monocytes ◽  
Activated T Cells ◽  
Cellular Origin

C1q deficiency is the strongest known risk factor for SLE (systemic lupus erythematosus) but its endogenous cellular origin remains limitedly understood. In the present study we investigate the production of C1q by both cultured and endogenous bone osteoclasts. Blood monocytes were cultured with RANKL (receptor activator of nuclear factor κB ligand) and M-CSF (macrophage colony-stimulating factor) to generate osteoclasts and these cells expressed C1Q mRNA and also secreted C1q protein. Intracellular C1q was detectable in developing osteoclasts at day 3 by Western blotting and was also detectable by flow cytometry. By immunofluorescence microscopy, C1q was preferentially detected in immature osteoclasts. By multiple detection methods, C1q expression was markedly increased after IFNγ (interferon γ) treatment. By immunohistochemistry, C1q was also detected in endogenous bone osteoclasts. When osteoclasts were cultured on immobilized C1q, these cells exhibited 2–7-fold increases in the expression of signature osteoclast genes [TRAP (tartrate-resistant acid phosphatase), cathepsin K, calcitonin receptor, carbonic anhydrase II and NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1)], suggesting an osteoclastogenic capability. This is the first report of C1q production by osteoclasts. Its ability to enhance osteoclast development implies reduced osteoclastogenesis in patients with SLE as they often experience decreased C1q levels. This is consistent with the non-erosive nature of lupus arthritis.

MALT1 directs B cell receptor–induced canonical nuclear factor-κB signaling selectively to the c-Rel subunit

2007 ◽  
Vol 8 (9) ◽  
pp. 984-991 ◽  
Author(s):  
Uta Ferch ◽  
Christian Meyer zum Büschenfelde ◽  
Andreas Gewies ◽  
Elmar Wegener ◽  
Sandra Rauser ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
B Cell Receptor ◽  
Nuclear Factor

scholarly journals T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry

2016 ◽  
Vol 291 (16) ◽  
pp. 8440-8452 ◽  
Author(s):  
Xiaohong Liu ◽  
Corbett T. Berry ◽  
Gordon Ruthel ◽  
Jonathan J. Madara ◽  
Katelyn MacGillivray ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Transcriptional Activation ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Calcium Entry ◽  
Nuclear Factor

B-cell antigen receptor activates transcription factors NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB) via a mechanism that involves diacylglycerol

2004 ◽  
Vol 32 (1) ◽  
pp. 113-115 ◽  
Author(s):  
P. Antony ◽  
J.B. Petro ◽  
G. Carlesso ◽  
N.P. Shinners ◽  
J. Lowe ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
B Cell ◽  
Antigen Receptor ◽  
Nuclear Factor Κb ◽  
B Cell Antigen Receptor ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Engagement of the B-cell antigen receptor (BCR) induces the activation of various transcription factors, including NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB), which participate in long-term biological responses such as proliferation, survival and differentiation of B-lymphocytes. We addressed the biochemical basis of this process using the DT40 chicken B-cell lymphoma. We discovered that Bruton's tyrosine kinase (BTK) and phospholipase C-γ2 (PLC-γ2) are required to activate NFAT and NF-κB, and to produce the lipid second messenger diacylglycerol in response to BCR cross-linking. Therefore the functional integrity of the BTK/PLC-γ2/diacylglycerol signalling axis is crucial for BCR-directed activation of both transcription factors NFAT and NF-κB.

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