Dataset Information

Clinical implications of CD4⁺ T cell subsets in adult atopic asthma patients.

ABSTRACT:

Background

T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood.

Methods

We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity.

Results

We report four major features of CD4⁺ T cells in the blood of atopic asthma patients. First, patients had a profound increase of CCR7⁺ memory CD4⁺ T cells, but not CCR7^- memory CD4⁺ T cells. Second, an increase in CCR4⁺ CD4⁺ T cells in patients was mainly attributed to the increase of CCR7⁺ memory CD4⁺ T cells. Accordingly, the frequency of CCR4⁺CCR7⁺ memory CD4⁺ T cells correlated with asthma severity. Current common asthma therapeutics (including corticosteroids) were not able to affect the frequency of CCR4⁺CCR7⁺ memory CD4⁺ T cell subsets. Third, patients had an increase of Tregs, as assessed by measuring CD25, Foxp3, IL-10 and CTLA-4 expression. However, asthma severity was inversely correlated only with the frequency of CTLA-4⁺ CD4⁺ T cells. Lastly, patients and control subjects have similar frequencies of CD4⁺ T cells that express CCR5, CCR6, CXCR3, CXCR5, CD11a, or α4 integrin. However, the frequency of α4⁺ CD4⁺ T cells in patients correlated with asthma severity.

Conclusions

CCR4⁺CCR7⁺ memory, but not CCR4⁺CCR7^- memory, α4⁺, and CTLA4⁺ CD4⁺ T cells in patients show significant clinical implications in atopic asthma. Current common therapeutics cannot alter the frequency of such CD4⁺ T cell subsets in adult atopic asthma patients.

SUBMITTER: Wiest M

PROVIDER: S-EPMC5833086 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Clinical implications of CD4<sup>+</sup> T cell subsets in adult atopic asthma patients.

Wiest Matthew M Upchurch Katherine K Yin Wenjie W Ellis Jerome J Xue Yaming Y Lanier Bobby B Millard Mark M Joo HyeMee H Oh SangKon S

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20180302

<h4>Background</h4>T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood.<h4>Methods</h4>We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity. ...[more]

PMID: 29507584

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Project description:BackgroundPerturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma.ResultsBacterial microbiota in paired protected bronchial brushings (BB; n = 45), induced sputum (IS; n = 45), oral wash (OW; n = 45), and nasal brushings (NB; n = 27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p < 0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r = 0.004 [- 0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p < 0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p = 0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation.ConclusionsInduced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.

Project description:CD4+ T cell subsets including regulatory T cells (Tregs), Th1 and Th17 are critical for control and development of inflammation and autoimmunity. We investigated the in vitro and in vivo effects of silymarin, a well-known herbal medicine on differentiation and function of Tregs and Th1 and Th17 responses. For in vitro study, mice splenocytes treated with 20-30 μg/ml silymarin were evaluated for gene expressions of specific transcription factors and cytokines of CD4+ T cell subsets using real-time PCR. Induction of Treg cell development in the presence of silymarin was performed on isolated naïve CD4+ T cells. Effect of silymarin-induced Tregs on T cell suppression was determined by CFSE labeling method. Results of this part showed that silymarin significantly decreased IFNγ, RORγt and IL-17 gene expressions and upregulated Foxp3, TGF-β and IL-10 mRNA. More silymarin-enhanced naïve CD4+ T cells differentiated to Tregs (67%) than the control (47%). Silymarin-induced Tregs reduced proliferation of naïve activated T cells (<50%). For in vivo study, mice were immunized with ovalbumin (Ova) on days 1 and 14. Silymarin (100 mg/Kg) was intraperitoneally administered two days before the first Ova challenge followed by on every day for two weeks. Splenocytes were then isolated for assessment of CD4+ T cell subsets and ex vivo analysis using flow cytometry. Treatment of Ova-immunized mice with silymarin increased Tregs (11.24 ± 1.2%, p < 0.01(but decreased Th1 (1.72 ± 0.4%, p < 0.001) and Th17 (1.07 ± 0.04%, p < 0.001) cells. Ex vivo Ova challenge of splenocytes from Ova-immunized mice treated with silymarin decreased proliferation of splenocytes, IFNγ (2.76% of control) and IL-17 (<8%) along with increased TGF-β (59.7%) expressions in CD4+T-bet+, CD4+RORγt+ and CD4+Foxp3+ T cells, respectively. In conclusion, silymarin promoted Treg differentiation and function and decreased Th1 and Th17 cells. Silymarin may differentially regulate CD4+ T cell responses which can provide potential benefits for its use as treatment of immune-related diseases. Graphical abstract ᅟ.

Dataset Information

Clinical implications of CD4⁺ T cell subsets in adult atopic asthma patients.

Background

Methods

Results

Conclusions

Publications

Clinical implications of CD4<sup>+</sup> T cell subsets in adult atopic asthma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Clinical implications of CD4+ T cell subsets in adult atopic asthma patients.

Background

Methods

Results

Conclusions

Publications

Clinical implications of CD4<sup>+</sup> T cell subsets in adult atopic asthma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Clinical implications of CD4⁺ T cell subsets in adult atopic asthma patients.