Allergen provocation increases TH2‐cytokines and FOXP3 expression in the asthmatic lung

Thunberg, Sarah; Gafvelin, Guro; Nord, Magnus; Grönneberg, R.; Grünewald, Johan; Eklúnd, Anders; Hage, Marianne van

doi:10.1111/j.1398-9995.2009.02218.x

Cited by 58 publications

(74 citation statements)

References 36 publications

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“…In particular, GATA3 expression was positively correlated with pSTAT6, which indicated a certain regulatory relationship between pSTAT6 and GATA3. As we know, pSTAT6 can be regulated by many factors in the body and change in pSTAT6 correlates with many diseases (Batra et al, 2004;Thunberg et al, 2010;Chen et al, 2013;Yao et al, 2013;Irvin et al, 2014). Our present results prove that after boswellic acid treatment, GATA3 is downregulated following a decrease in pSTAT6, which indicates that boswellic acid may improve the asthma phenotype by inhibiting pSTAT6 and thus influencing GATA3 expression (Tachdjian et al, 2010).…”

Section: Discussionsupporting

confidence: 69%

Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6

Zhou

et al. 2015

Genet. Mol. Res.

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ABSTRACT.To study the role of boswellic acid in reducing asthma phenotype severity and the relationship between the expression of pSTAT6 and GATA3, thirty-six mice were randomly divided into normal control group, asthma group, and boswellic acid group (treatment group). The asthma model was established through an intraperitoneal injection of sensitization liquid (0.15 mL aluminum hydroxide gel at 88.67 mg/ mL and 0.05 mg ovalbumin). pSTAT6 and GATA3 expression levels in peripheral blood were detected by reverse transcription-polymerase chain reaction and Western blot analysis. pSTAT6 and GATA3 gene expressions in the asthmatic group were significantly higher than in the normal control group; they were markedly lower in the treatment group than the asthma group, and there was no significant difference when compared with the normal control group. The pSTAT6 expressions in the asthma, control and treatment groups were 2.256 ± 0.125, 0.524 ± 0.210, and 0.897 ± 0.134 at gray level, respectively. The GATA3 expressions in the asthma, control, and treatment groups were 3.521 X. Zhou et al. 7464©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 7463-7468 (2015) ± 0.631, 0.435 ± 0.136, and 0.743 ± 0.149 at gray level, respectively. pSTAT6 and GATA3 expression levels were similar in the treatment and control groups. GATA3 expression had a positive correlation with pSTAT6 expression. Boswellic acid may improve asthma symptoms by inhibiting pSTAT6 expression, which consequently reduces GATA3 expression.

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Section: Discussionsupporting

confidence: 69%

Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6

Zhou

et al. 2015

Genet. Mol. Res.

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“…Allergic responses in the lung are traditionally thought of as being Th2 mediated; however, recent studies have shown that IL-9 contributes to allergic responses by promoting mast cell expansion and production of IL-13, which stimulates the release of mucus and contributes to airway hyperresponsiveness (1,5,8,9). Serum IL-9 levels, which correlate with symptom severity in patients with allergic rhinitis, depend on exposure to a causal allergen (10)(11)(12)(13)(14). Similarly, during the effector phase of food allergy, IL-9 promotes mastocytosis, which increases intestinal permeability (15).…”

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confidence: 99%

Cyclooxygenase-2 Inhibits T Helper Cell Type 9 Differentiation during Allergic Lung Inflammation via Down-regulation of IL-17RB

Li¹,

Edin²,

Bradbury³

et al. 2013

Am J Respir Crit Care Med

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Rationale: HelperCD41 T cell subsets, includingIL-9-and IL-10-producing T helper cell type 9 (Th9) cells, exist under certain inflammatory conditions. Cyclooxygenase (COX)-1 and COX-2 play important roles in allergic lung inflammation and asthma. It is unknown whether COX-derived eicosanoids regulate Th9 cells during allergic lung inflammation. Objectives: To determine the role of COX metabolites in regulating Th9 cell differentiation and function during allergic lung inflammation., COX-2 2/2 , and wild-type (WT) mice were studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of Th9 differentiation using flow cytometry, cytokine assays, confocal microscopy, real-time PCR, and immunoblotting. In addition, the role of specific eicosanoids and their receptors was examined using synthetic prostaglandins (PGs), selective inhibitors, and siRNA knockdown. Measurements and Main Results: Experimental endpoints were not different between COX-1 2/2 and WT mice; however, the percentage of IL-9 1 CD4 1 T cells was increased in lung, bronchoalveolar lavage fluid, lymph nodes, and blood of allergic COX-2 2/2 mice relative to WT. Bronchoalveolar lavage fluid IL-9 and IL-10, serum IL-9, and lung IL-17RB levels were significantly increased in allergic COX-2 2/2 mice or in WT mice treated with COX-2 inhibitors. IL-9, IL-10, and IL-17RB expression in vivo was inhibited by PGD 2 and PGE 2 , which also reduced Th9 cell differentiation of murine and human naive CD4 1 T cells in vitro. Inhibition of protein kinase A significantly increased Th9 cell differentiation of naive CD4 1 T cells isolated from WT mice in vitro. Conclusions: COX-2-derived PGD 2 and PGE 2 regulate Th9 cell differentiation by suppressing IL-17RB expression via a protein kinase A-dependent mechanism.

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“…Uncontrolled effector T cell responses may result in excessive inflammation and, eventually, in host pathology. In this regard, Th1 and Th17 cells have been associated with various human autoimmune conditions, such as multiple sclerosis (1) and inflammatory bowel disease (2), whereas Th2 cells have been implicated in the development of human allergic asthma (3). Given that CD4 + T cells not only play a key role in protecting the organism from various threats but are also potentially harmful to self-tissues, their function needs to be under stringent control.…”

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confidence: 99%

Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity

Contreras

Prado

González

et al. 2016

The Journal of Immunology

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Dopamine receptor D3 (DRD3) expressed on CD4+ T cells is required to promote neuroinflammation in a murine model of Parkinson’s disease. However, how DRD3 signaling affects T cell–mediated immunity remains unknown. In this study, we report that TCR stimulation on mouse CD4+ T cells induces DRD3 expression, regardless of the lineage specification. Importantly, functional analyses performed in vivo using adoptive transfer of OVA-specific OT-II cells into wild-type recipients show that DRD3 deficiency in CD4+ T cells results in attenuated differentiation of naive CD4+ T cells toward the Th1 phenotype, exacerbated generation of Th2 cells, and unaltered Th17 differentiation. The reciprocal regulatory effect of DRD3 signaling in CD4+ T cells favoring Th1 generation and impairing the acquisition of Th2 phenotype was also reproduced using in vitro approaches. Mechanistic analysis indicates that DRD3 signaling evokes suppressor of cytokine signaling 5 expression, a negative regulator of Th2 development, which indirectly favors acquisition of Th1 phenotype. Accordingly, DRD3 deficiency results in exacerbated eosinophil infiltration into the airways of mice undergoing house dust mite–induced allergic response. Interestingly, our results show that, upon chronic inflammatory colitis induced by transfer of naive CD4+ T cells into lymphopenic recipients, DRD3 deficiency not only affects Th1 response, but also the frequency of Th17 cells, suggesting that DRD3 signaling also contributes to Th17 expansion under chronic inflammatory conditions. In conclusion, our findings indicate that DRD3-mediated signaling in CD4+ T cells plays a crucial role in the balance of effector lineages, favoring the inflammatory potential of CD4+ T cells.

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Allergen provocation increases TH2‐cytokines and FOXP3 expression in the asthmatic lung

Abstract: Despite an increase in CD4(+)CD25(bright) cells expressing high levels of FOXP3 in response to bronchial allergen provocation, asthmatic patients exhibit enhanced levels of Th2 cytokines in the lung, which may indicate an inability among infiltrating cells to suppress Th2 responses.

Cited by 58 publications

References 36 publications

Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6

Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6

Cyclooxygenase-2 Inhibits T Helper Cell Type 9 Differentiation during Allergic Lung Inflammation via Down-regulation of IL-17RB

Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity

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