scholarly journals IL-2 Modulates Th2 cell Responses to Glucocorticoid: A Cause of Persistent Type 2 Inflammation?

2018 ◽  
Author(s):  
Tharsan Kanagalingam ◽  
Meerah Vijeyakumaran ◽  
Nami Shrestha Palikhe ◽  
Lauren Solomon ◽  
Harissios Vliagoftis ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Asthma Severity ◽  
Th2 Cells ◽  
Peripheral Blood Cells ◽  
Cell Responses ◽  
Th2 Cell ◽  
Type 2 Inflammation

ABSTRACTBackgroundInhaled glucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine (IL-4, IL-5 and IL-13) expression and induce apoptosis. Asthma severity is associated with GC insensitivity, increased type 2 inflammation and circulating Th2 cells. Since IL-2 is a T cell survival factor, we assessed whether IL-2 levels associate with the proportion of Th2 cells and/or correlate with clinical features of asthma severity.MethodsPeripheral blood from asthma patients (n=18) was obtained and Th2 cell numbers determined by flow cytometry. Peripheral blood cells were activated with mitogen (24hrs) and supernatant levels of IL-2 and IL-13 measured by ELISA. In vitro differentiated Th2 cells were treated with dexamethasone and IL-2 and assessed for apoptosis by flow cytometry staining of Annexin V. Level of mRNA for anti-apoptotic (BCL-2) and pro-apoptotic (BIM) genes as well as IL-13 were determined by qRT-PCR.ResultsIL-2 produced by activated peripheral blood cells correlated negatively with lung function (FEV1) and positively with daily dose of inhaled GC. When patients were stratified based on IL-2 level, high IL-2 producers made more IL-13 and had more circulating Th2 cells. In vitro, increasing the level of IL-2 in the culture media was associated with resistance to DEX-induced apoptosis, more BCL-2 and less BIM mRNA. Th2 cells cultured with higher IL-2 also had more IL-13 mRNA and required higher concentrations of DEX for cytokine suppression.Conclusions and Clinical RelevanceIL-2 modulates Th2 cell responses to GC, supporting both their survival and pro-inflammatory capacity, suggesting that a patient’s potential to produce IL-2 may be a determinant in asthma severity.

scholarly journals ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Jiang ◽  
Ren Cai ◽  
Jing Wang ◽  
Zheng Li ◽  
Dan Xu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Peripheral Blood ◽  
Culture Supernatant ◽  
Th2 Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Protein Levels ◽  
Th2 Cell

This study is to investigate the capacity of type 2 innate lymphoid cells (ILC2s) in regulating the Th2 type adaptive immune response of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study enrolled healthy people, stable chronic obstructive pulmonary disease (COPD) patients, and AECOPD patients. Flow cytometry was used to detect Th2 and ILC2 cells in the peripheral blood. In addition, ILC2s from the peripheral blood of AECOPD patients were stimulated with PBS, IL-33, Jagged1, DAPT, IL-33+Jagged1, IL-33+DAPT, and IL-33+Jagged-1+DAP in vitro. The levels of cytokines in the culture supernatant were detected by ELISA and the culture supernatant was used to culture CD4 + T cells. The mRNA and protein levels of Notch1, hes1, GATA3, RORα, and NF-κB of ILC2s were detected by real-time PCR and Western blot. The proportion of Th2 and ILC2s was significantly increased in the peripheral blood of AECOPD patients, alone with the increased Notch1, hes1, and GATA3 mRNA levels. In vitro results showed that the mRNA and protein levels of Notch1, hes1, GATA3 and NF-κB were significantly increased after stimulation with Notch agonist, meanwhile, the level of type 2 cytokines were increased in the supernatant of cells stimulated with Notch agonist, and significantly promoted differentiation of Th2 cells in vitro. Disruption of Notch pathway weakened GATA3 expression and cytokine production, and ultimately affected the differentiation of Th2 cells. In conclusion, our results suggest that ILC2s can promote Th2 cell differentiation in AECOPD via activated Notch-GATA3 signal pathway.

scholarly journals Dual Activation of Estrogen Receptor Alpha and Glucocorticoid Receptor Upregulate CRTh2-Mediated Type 2 Inflammation; Mechanism Driving Asthma Severity in Women?

2021 ◽  
Author(s):  
Nami Shrestha Palikhe ◽  
Meerah Vijeyakumaran ◽  
Jenna Fortunato ◽  
Lauren Solomon ◽  
Harissios Vliagoftis ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Severe Asthma ◽  
Estrogen Receptor Alpha ◽  
Annexin V ◽  
Th2 Cells ◽  
Receptor Alpha ◽  
Th2 Cell ◽  
Type 2 Inflammation

Background: Type 2-high asthma is characterized by elevated levels of circulating Th2 cells and eosinophils, cells that express chemoattractant-homologous receptor expressed on Th2 cells (CRTh2). Severe asthma is more common in women than men; however, the underlying mechanism(s) remain elusive. Here we examined whether the relationship between severe asthma and type 2 inflammation differs by sex and if estrogen influences Th2 cell response to glucocorticoid (GC). Methods: Type 2 inflammation and the proportion of blood Th2 cells (CD4 CRTh2 ) were assessed in whole blood from subjects with asthma (n = 66). The effects of GC and estrogen receptor alpha (ERα) agonist on in vitro differentiated Th2 cells were examined. Expression of CRTh2, type 2 cytokines and degree of apoptosis (Annexin V , 7-AAD) were determined by flow cytometry, qRT-PCR, western blot and ELISA. Results: In severe asthma, the proportion of circulating Th2 cells and hospitalizations were higher in women than men. Women with severe asthma also had more Th2 cells and serum IL-13 than women with mild/moderate asthma. Th2 cells, eosinophils and CRTh2 mRNA correlated with clinical characteristics associated with asthma control in women but not men. In vitro, GC and ERα agonist treated Th2 cells exhibited less apoptosis, more CRTh2 as well as IL-5 and IL-13 following CRTh2 activation than Th2 cells treated with GC alone. Conclusion: Women with severe asthma had higher levels of circulating Th2 cells than men, which may be due to estrogen modifying the effects of GC, enhancing Th2 cell survival and type 2 cytokine production. (249)

Comparison of cytarabine, mitoxantrone, and CNDAC in vitro treatment of AML bone marrow and peripheral blood cells.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 6588-6588
Author(s):  
S. Jagan ◽  
L. A. Paganessi ◽  
S. Gezer ◽  
A. Rizman ◽  
D. Rifai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Peripheral Blood Cells ◽  
In Vitro Treatment

In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood cells: Role of suppressor T cells in normal subjects

Neurology ◽  
1984 ◽  
Vol 34 (6) ◽  
pp. 802-802 ◽  
Author(s):  
R. P. Lisak ◽  
C. Laramore ◽  
A. I. Levinson ◽  
B. Zweiman ◽  
A. R. Moskovitz ◽  
...  
Keyword(s):  
T Cells ◽  
Acetylcholine Receptor ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Normal Subjects ◽  
Peripheral Blood Cells ◽  
Suppressor T Cells ◽  
In Vitro Synthesis

scholarly journals Detection of adeno-associated virus type 2 in human peripheral blood cells

1992 ◽  
Vol 73 (4) ◽  
pp. 961-966 ◽  
Author(s):  
Z. Grossman ◽  
E. Mendelson ◽  
F. Brok-Simoni ◽  
F. Mileguir ◽  
Y. Leitner ◽  
...  
Keyword(s):  
Virus Type ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Cells ◽  
Adeno Associated Virus
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