scholarly journals Potential Mechanisms of T Cell-Mediated and Eosinophil-Independent Bronchial Hyperresponsiveness

2019 ◽  
Vol 20 (12) ◽  
pp. 2980 ◽  
Author(s):  
Mayumi Saeki ◽  
Tomoe Nishimura ◽  
Noriko Kitamura ◽  
Takachika Hiroi ◽  
Akio Mori ◽  
...  
Keyword(s):  
T Cell ◽  
Bronchial Asthma ◽  
Inhaled Corticosteroids ◽  
Bronchial Hyperresponsiveness ◽  
T Cell Subsets ◽  
Eosinophil Infiltration ◽  
Mucus Production ◽  
Th2 Cell ◽  
Reversible Airway Obstruction ◽  
Th9 Cells

Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.

scholarly journals Glutamine metabolism regulates Th2 cell differentiation via the α-ketoglutalate-dependent demethylation of histone H3K27

2017 ◽  
Author(s):  
Makoto Kuwahara ◽  
Maya Izumoto ◽  
Hiroaki Honda ◽  
Kazuki Inoue ◽  
Yuuki Imai ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Gene Locus ◽  
Glutamine Metabolism ◽  
T Cell Subsets ◽  
Cytokine Gene ◽  
Th2 Cytokine ◽  
Th2 Cell ◽  
Histone H3k27 ◽  
The Impact

AbstractThe acquisition of T cell functions seems to be closely linked to the reprogramming of the metabolic pathway. However, the impact of metabolic changes on the differentiation of helper T cell subsets remains unclear. We found that TCR-mediated activation of glutamine metabolism regulates Th2 cell differentiation via the supplementation of α-ketogulutalate (α-KG) and histone H3K27 demethylation. Deprivation of glutamine or pharmacological inhibition of glutamine metabolism blocks the induction of Th2 cell differentiation without affecting Stat6 phosphorylation. The methylation status of H3K27 at the Th2 cytokine gene locus was significantly increased in Th2 cells cultured under glutamine-deprived conditions. The inhibitory effect of glutamine-deprivation was antagonized by α-KG, and the α-KG-dependent induction of Th2 cell differentiation was reduced in utx- and jmjd3-deficient naïve CD4 T cells. These findings show that the glutamine-a-ketoglutarate axis is crucial to regulating the epigenetic status at the Th2 cytokine gene locus and subsequent Th2 cell differentiation.

Inhalation of sphingosine kinase inhibitor attenuates airway inflammation in asthmatic mouse model

2008 ◽  
Vol 294 (6) ◽  
pp. L1085-L1093 ◽  
Author(s):  
Teruaki Nishiuma ◽  
Yoshihiro Nishimura ◽  
Taro Okada ◽  
Emi Kuramoto ◽  
Yoshikazu Kotani ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bronchial Asthma ◽  
Kinase Inhibitor ◽  
Mrna Level ◽  
Bronchial Hyperresponsiveness ◽  
Sphingosine Kinase ◽  
Inhibitory Effect ◽  
Eosinophil Infiltration ◽  
Cell Hyperplasia ◽  
Sphingosine 1 Phosphate

Sphingosine 1-phosphate (S1P) produced by sphingosine kinase (SPHK) is implicated in acute immunoresponses, however, mechanisms of SPHK/S1P signaling in the pathogenesis of bronchial asthma are poorly understood. In this study, we hypothesized that SPHK inhibition could ameliorate lung inflammation in ovalbumin (OVA)-challenged mouse lungs. Six- to eight-week-old C57BL/6J mice were sensitized and exposed to OVA for 3 consecutive days. Twenty-four hours later, mice lungs and bronchoalveolar lavage (BAL) fluid were analyzed. For an inhibitory effect, either of the two different SPHK inhibitors, N, N-dimethylsphingosine (DMS) or SPHK inhibitor [SK-I; 2-( p-hydroxyanilino)-4-( p-chlorophenyl) thiazole], was nebulized for 30 min before OVA inhalation. OVA inhalation caused S1P release into BAL fluid and high expression of SPHK1 around bronchial epithelial walls and inflammatory areas. DMS or SK-I inhalation resulted in a decrease in S1P amounts in BAL fluid to basal levels, accompanied by decreased eosinophil infiltration and peroxidase activity. The extent of inhibition caused by DMS inhalation was higher than that caused by SK-I. Like T helper 2 (Th2) cytokine release, OVA inhalation-induced increase in eotaxin expression was significantly suppressed by DMS pretreatment both at protein level in BAL fluid and at mRNA level in lung homogenates. Moreover, bronchial hyperresponsiveness to inhaled methacholine and goblet cell hyperplasia were improved by SPHK inhibitors. These data suggest that the inhibition of SPHK affected acute eosinophilic inflammation induced in antigen-challenged mouse model and that targeting SPHK may provide a novel therapeutic tool to treat bronchial asthma.

T-Cell Subsets in Female Sexual Partners of Asymptomatic Hemophiliacs

1984 ◽  
Vol 51 (01) ◽  
pp. 135-135
Author(s):  
Ingrid Pabinger-Fasching ◽  
Klaus Lechner ◽  
Peter Bettelheim ◽  
Herwig Niessner ◽  
Ursula Köller ◽  
...  
Keyword(s):  
T Cell ◽  
Sexual Partners ◽  
T Cell Subsets

Aberrant activation of CD8+ T-cell and CD8+ T-cell subsets in patients with newly diagnosed IDDM

Diabetes ◽  
1995 ◽  
Vol 44 (12) ◽  
pp. 1414-1419 ◽  
Author(s):  
B. Hehmke ◽  
D. Michaelis ◽  
E. Gens ◽  
F. Laube ◽  
K. D. Kohnert
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
Newly Diagnosed
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