HEMORRHAGE (HEM) UNLIKE SEPSIS DOES NOT INDUCE OVERT EX VIVO LYMPHOID CELL APOPTOSIS

Shock ◽  
1995 ◽  
Vol 3 (6) ◽  
pp. 43
Author(s):  
A. Ayala ◽  
C. D. Herdon ◽  
I. H. Chaudry
Keyword(s):  
Lymphoid Cell ◽  
Cell Apoptosis ◽  
Ex Vivo

HEMORRHAGE (HEM) UNLIKE SEPSIS DOES NOT INDUCE OVERT EX VIVO LYMPHOID CELL APOPTOSIS.

Shock ◽  
1995 ◽  
Vol 3 ◽  
pp. 43-44
Author(s):  
A. Ayala ◽  
C. D. Herdon ◽  
I. H. Chaudry
Keyword(s):  
Lymphoid Cell ◽  
Cell Apoptosis ◽  
Ex Vivo

Regulation of Lymphoid Cell Apoptosis by Jaks and Stats;

2004 ◽  
Vol 24 (2) ◽  
pp. 87-110 ◽  
Author(s):  
Zsuzsanna S. Nagy ◽  
Jeremy Ross ◽  
Hanyin Cheng ◽  
Stanislaw M. Stepkowski ◽  
Robert A. Kirken
Keyword(s):  
Lymphoid Cell ◽  
Cell Apoptosis

Anti-CD20 mAb-Induced B Cell Apoptosis Generates T Cell Regulation of Experimental Myeloperoxidase ANCA-Associated Vasculitis

2021 ◽  
pp. ASN.2020060834
Author(s):  
Poh-Yi Gan ◽  
Jonathan Dick ◽  
Kim M. O’Sullivan ◽  
Virginie Oudin ◽  
Anne Cao Le ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Apoptosis ◽  
T Regulatory Cells ◽  
Ex Vivo ◽  
Therapeutic Benefit ◽  
Anca Associated Vasculitis ◽  
Splenic Macrophages ◽  
Humoral Autoimmunity ◽  
Anti Cd20

BackgroundMyeloperoxidase ANCA-associated vasculitis is a major cause of ESKD. Efficacy of anti-CD20 mAb treatment was tested in a mouse model of the disease.MethodsMPO immunization induced anti-MPO autoimmunity, and a subnephritogenic dose of sheep anti-mouse GBM globulin triggered GN.ResultsAnti-CD20 mAb treatment increased the numbers and immunomodulatory capacity of MPO-specific T regulatory cells (Tregs) and attenuated T cell–mediated and humoral anti-MPO autoimmunity and GN. Disabling of Tregs negated the therapeutic benefit of anti-CD20 treatment. The mechanism of enhancement of Treg activity could be attributed to anti-CD20 mAb effects on inducing B cell apoptosis. Administering anti-CD20 mAb-induced apoptotic splenocytes to mice developing anti-MPO GN was as effective as anti-CD20 mAb treatment in inducing Tregs and attenuating both anti-MPO autoimmunity and GN. A nonredundant role for splenic macrophages in mediating the anti-CD20 mAb-induced immunomodulation was demonstrated by showing that administration of anti-CD20 mAb ex vivo–induced apoptotic splenocytes to unmanipulated mice attenuated autoimmunity and GN, whereas deletion of splenic marginal zone macrophages prevented anti-CD20 mAb-induced immunomodulation and treatment efficacy. Six days after administering anti-CD20 mAb to mice with murine anti-MPO GN, cell-mediated anti-MPO responses and GN were attenuated, and Tregs were enhanced, but ANCA levels were unchanged, suggesting humoral autoimmunity was redundant at this time point.ConclusionsCollectively, these data suggest that, as well as reducing humoral autoimmunity, anti-CD20 mAb more rapidly induces protective anti-MPO Treg-mediated immunomodulation by splenic processing of anti-CD20–induced apoptotic B cells.

scholarly journals Differential Modulation of Human Innate Lymphoid Cell (ILC) Subsets by IL-10 and TGF-β

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sandra Bonne-Année ◽  
Mabel C. Bush ◽  
Thomas B. Nutman
Keyword(s):  
Lymphoid Cell ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Low Frequency ◽  
Surface Expression ◽  
Multiparameter Flow Cytometry ◽  
Innate Lymphoid Cell ◽  
Low Frequencies ◽  
Immunoregulatory Cytokines ◽  
Ifn Γ

Abstract Using multiparameter flow cytometry human innate lymphoid cell (ILC) subsets can be detected in the circulation, in relatively low frequencies. Despite the low frequency of ILCs in circulation, ex vivo experiments have demonstrated that these ILCs release extremely large per cell quantities of signature ILC cytokines following activation. To determine how activated ILC cytokine production is regulated, ILC subsets were activated in the presence or absence of the immunoregulatory cytokines IL-10 and TGF-β. An examination of circulating ILC subsets revealed surface expression of IL-10Rα and mRNA expression of both IL-10Rα and TGF-βR1 for all ILC subsets. Stimulated ILC1 production of IFN-γ was decreased by TGF-β and not IL-10. Interestingly, ILC2s stimulated in the presence of IL-10 had a marked reduction in cytokine production of IL-5 and IL-13 while TGF-β had no effect on ILC2 cytokine production. Ex vivo activated ILC1 and ILC2 subsets were also found to be a source of the immunoregulatory cytokine IL-10, raising the potential for ILC-mediated regulation of immune cells. These findings demonstrate the differential effects of immunoregulatory cytokines IL-10 and TGF-β on activated ILC1 and ILC2 populations ex vivo.

IRF6 and TAK1 coordinately promote the activation of HIPK2 to stimulate apoptosis during palate fusion

2019 ◽  
Vol 12 (593) ◽  
pp. eaav7666 ◽  
Author(s):  
Chen-Yeh Ke ◽  
Hua-Hsuan Mei ◽  
Fen-Hwa Wong ◽  
Lun-Jou Lo
Keyword(s):  
Transcription Factor ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Human Cancer ◽  
Ectopic Expression ◽  
Interacting Protein ◽  
Human Cancer Cells

Cleft palate is a common craniofacial defect caused by a failure in palate fusion. The palatal shelves migrate toward one another and meet at the embryonic midline, creating a seam. Transforming growth factor–β3 (TGF-β3)–induced apoptosis of the medial edge epithelium (MEE), the cells located along the seam, is required for completion of palate fusion. The transcription factor interferon regulatory factor 6 (IRF6) promotes TGF-β3–induced MEE cell apoptosis by stimulating the degradation of the transcription factor ΔNp63 and promoting the expression of the gene encoding the cyclin-dependent kinase inhibitor p21. Because homeodomain-interacting protein kinase 2 (HIPK2) functions downstream of IRF6 in human cancer cells and is required for ΔNp63 protein degradation in keratinocytes, we investigated whether HIPK2 played a role in IRF6-induced ΔNp63 degradation in palate fusion. HIPK2 was present in the MEE cells of mouse palatal shelves during seam formation in vivo, and ectopic expression of IRF6 in palatal shelves cultured ex vivo stimulated the expression of Hipk2 and the accumulation of phosphorylated HIPK2. Knockdown and ectopic expression experiments in organ culture demonstrated that p21 was required for HIPK2- and IRF6-dependent activation of caspase 3, MEE apoptosis, and palate fusion. Contact between palatal shelves enhanced the phosphorylation of TGF-β–activated kinase 1 (TAK1), which promoted the phosphorylation of HIPK2 and palate fusion. Our findings demonstrate that HIPK2 promotes seam cell apoptosis and palate fusion downstream of IRF6 and that IRF6 and TAK1 appear to coordinately enhance the abundance and activation of HIPK2 during palate fusion.

Odontoblastic Exosomes Attenuate Apoptosis in Neighboring Cells

2019 ◽  
Vol 98 (11) ◽  
pp. 1271-1278 ◽  
Author(s):  
H.S. Wang ◽  
F.H. Yang ◽  
Y.J. Wang ◽  
F. Pei ◽  
Z. Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Dental Pulp ◽  
Ex Vivo ◽  
Intercellular Signaling ◽  
High Concentration ◽  
Rescue Effect ◽  
Apical Papilla ◽  
External Stimuli

Each odontoblast is tightly linked to other odontoblasts. They form a line of defense and are capable of withstanding external stimuli, particularly the inflammation caused by caries. Thus, we investigated exosomes derived from odontoblasts as an intercellular mechanism by which inflamed odontoblasts are protected from apoptosis. CD63, an exosome marker, was expressed at high levels in caries-affected regions of the dental pulp. We conducted an ex vivo experiment by applying different concentrations of lipopolysaccharide (LPS) to the odontoblast-like cells (mineralization was induced in stem cells derived from the apical papilla). Odontoblast-like cells treated with a high concentration of LPS (20 µg/mL LPS, severely affected) exhibited an accelerated release of exosomes, which attenuated the LPS-induced cell apoptosis of odontoblast-like cells treated with a low concentration of LPS (1 µg/mL LPS, mildly affected). Next, we blocked exosome uptake with chlorpromazine, and the rescue effect vanished. Based on our findings, severely inflamed odontoblasts attenuate the apoptosis of mildly inflamed neighboring cells through an exosome-mediated intercellular signaling pathway.

scholarly journals 28S ribosome degradation in lymphoid cell apoptosis: evidence for caspase and Bcl-2-dependent and -independent pathways

2000 ◽  
Vol 7 (10) ◽  
pp. 994-1001 ◽  
Author(s):  
K L King ◽  
C M Jewell ◽  
C D Bortner ◽  
J A Cidlowski
Keyword(s):  
Lymphoid Cell ◽  
Cell Apoptosis

Novel targets for endoplasmic reticulum stress-induced apoptosis in B-CLL

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2713-2723 ◽  
Author(s):  
Emanuela Rosati ◽  
Rita Sabatini ◽  
Giuliana Rampino ◽  
Filomena De Falco ◽  
Mauro Di Ianni ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Ex Vivo ◽  
Lymphocytic Leukemia ◽  
Minor Role ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Induced Apoptosis

Abstract A better understanding of apoptotic signaling in B-chronic lymphocytic leukemia (B-CLL) cells may help to define new therapeutic strategies. This study investigated endoplasmic reticulum (ER) stress signaling in spontaneous apoptosis of B-CLL cells and whether manipulating ER stress increases their apoptosis. Results show that a novel ER stress-triggered caspase cascade, initiated by caspase-4 and involving caspase-8 and -3, plays an important role in spontaneous B-CLL cell apoptosis. ER stress-induced apoptosis in B-CLL cells also involves CHOP/GADD153 up-regulation, increased JNK1/2 phosphorylation, and caspase-8–mediated cleavage of Bap31 to Bap20, known to propagate apoptotic signals from ER to mitochondria. In ex vivo B-CLL cells, some apoptotic events associated with mitochondrial pathway also occur, including mitochondrial cytochrome c release and caspase-9 processing. However, pharmacologic inhibition studies show that caspase-9 plays a minor role in B-CLL cell apoptosis. ER stress also triggers survival signals in B-CLL cells by increasing BiP/GRP78 expression. Manipulating ER signaling by siRNA down-regulation of BiP/GRP78 or treating B-CLL cells with 2 well-known ER stress-inducers, tunicamycin and thapsigargin, increases their apoptosis. Overall, our findings show that ER triggers an essential pathway for B-CLL cell apoptosis and suggest that genetic and pharmacologic manipulation of ER signaling could represent an important therapeutic strategy.

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