Mesenchymal Stem Cell-Derived Exosome-Containing Linc00632 Regulates GATA Binding Protein-3 Expression in Allergic Rhinitis by Interacting with Enhancer of Zeste Homolog 2 to Inhibit T Helper Cell 2 Differentiation

2021 ◽  
pp. 1-11
Author(s):  
Wei Li ◽  
Cui-Yun Cai ◽  
Jun-Jie Zeng
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Nasal Mucosa ◽  
Binding Protein ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Th2 Differentiation

<b><i>Background:</i></b> Allergic rhinitis (AR) is regarded as one of the most common allergic disease of nasal mucosa affecting many people worldwide. Long noncoding RNAs are critical modulators affecting AR progression, whereas the pathogenesis of Linc00632 in the development of AR remains unclear. <b><i>Methods:</i></b> T helper cell 2 (Th2) differentiation of CD4<sup>+</sup> T cells was measured by flow cytometry. Real-time quantitative PCR assay and Western blot were applied to determine the levels of RNA and proteins, respectively. The interleukin (IL)-4 and IL-13 levels were quantitatively assessed through ELISA. Subcellular fractionation was conducted to detect the cellular localization of Linc00632. RNA immunoprecipitation experiment was employed to validate the interaction relationship between Linc00632 and enhancer of zeste homolog 2 (EZH2). Chromatin immunoprecipitation assay was used for determination of protein-DNA interactions. <b><i>Results:</i></b> The expression of Linc00632 was significantly decreased by 4 times in nasal mucosa of AR patients. Human umbilical cord mesenchymal stem cell-derived exosome dramatically inhibited Th2 differentiation, decreased GATA binding protein-3 (GATA-3) protein expressions and IL-4 levels by about 2 times in CD4<sup>+</sup> T cells. Knockdown Linc00632 partially reversed the effects of exosomes on Th2 differentiation, IL-4 and IL-13 levels, and GATA-3 expression. Linc00632 overexpression could suppress Th2 differentiation of CD4<sup>+</sup> T cells, reduced IL-4 and IL-13 levels, and GATA-3 expressions roughly 2 times. Linc00632 repressed the expression of GATA-3 by interacting with EZH2. GATA-3 overexpression partially reversed the effect of Linc00632 on Th2 differentiation of CD4<sup>+</sup> T cells. <b><i>Conclusion:</i></b> Linc00632 acted as a suppression factor in Th2 differentiation by inhibiting the expression of GATA-3 via interacting with EZH2, which might provide a new insight for understanding the action mechanism of Linc00632 in AR.

Expansion of HCV-specific T cells with a follicular T helper cell phenotype after DAA mediated antigen removal

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
M Smits ◽  
C Fauvelle ◽  
T Baumert ◽  
C Neumann-Haefelin ◽  
R Thimme ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Cell Phenotype ◽  
T Helper ◽  
Antigen Removal

scholarly journals Generation of IL-8 and IL-9 Producing CD4+T Cells Is Affected by Th17 Polarizing Conditions and AHR Ligands

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Michaela Gasch ◽  
Tina Goroll ◽  
Mario Bauer ◽  
Denise Hinz ◽  
Nicole Schütze ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Immune Cell ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Helper Cells ◽  
Aryl Hydrocarbon

The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells underin vitroconditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR) has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines. We found that a high proportion of T helper cells cultured under Th17 polarizing conditions are IL-8 and IL-9 single producing cells and that AHR activation results in an upregulation of IL-8 and a downregulation of IL-9 production. Thus, we have identified IL-8 and IL-9 producing T helper cells which are subject to regulation by the engagement of the AHR.

scholarly journals Anti–Interleukin 10 Receptor Monoclonal Antibody Is an Adjuvant for T Helper Cell Type 1 Responses to Soluble Antigen Only in the Presence of Lipopolysaccharide

2000 ◽  
Vol 192 (10) ◽  
pp. 1529-1534 ◽  
Author(s):  
Antonio G. Castro ◽  
Margaret Neighbors ◽  
Stephen D. Hurst ◽  
Francesca Zonin ◽  
Regina A. Silva ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Transfer Model ◽  
Soluble Antigen ◽  
Cell Type ◽  
T Helper ◽  
Peptide Antigen ◽  
Helper Cell Type

Soluble foreign antigen usually leads to a transient clonal expansion of antigen-specific T cells followed by the deletion and/or functional inactivation of the cells. As interleukin (IL)-10 is a key immunoregulatory cytokine, we questioned whether neutralization of IL-10 during priming with soluble antigen could prime for a subsequent T helper cell type 1 (Th1) effector recall response. By using an adoptive transfer model to track the fate of antigen-specific T cell receptor (TCR)-transgenic CD4+ T cells, we show that administration of soluble ovalbumin (OVA) protein, but not OVA323–339 peptide antigen, together with an anti–IL-10 receptor (R) mAb led to the enhancement of a Th1 response upon rechallenge. Lipopolysaccharide (LPS) present in the protein was necessary for priming for Th1 recall responses in the presence of anti–IL-10R mAb, as removal of LPS abrogated this effect. Moreover, addition of LPS to the peptide did not itself allow priming for recall Th1 effector responses unless endogenous levels of IL-10 were neutralized with an anti–IL-10R mAb. A significant increase in OVA-specific IgG1 and IgG2a isotypes was observed when the protein antigen was administered with anti–IL-10R mAb; however, this was not the case with peptide antigen administered together with anti–IL-10R and LPS. Our data, showing that LPS receptor signaling and neutralization of endogenous immunosuppressive cytokines is essential for Th1 priming, has important implications for the design of relevant vaccines for effective in vivo immunotherapy.

scholarly journals T helper cell polarisation as a measure of the maturation of the immune response

2003 ◽  
Vol 12 (5) ◽  
pp. 285-292 ◽  
Author(s):  
Scott B. Cameron ◽  
Ellen H. Stolte ◽  
Anthony W. Chow ◽  
Huub F. J. Savelkoul
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Intracellular Cytokine Staining ◽  
T Helper Cell ◽  
Helper Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intracellular Cytokine ◽  
T Helper

Background:T helper cell polarisation is important under chronic immune stimulatory conditions and drives the type of the evolving immune response. Mice treated with superantigensin vivodisplay strong effects on Thsubset differentiation. The aim of the study was to detect the intrinsic capacity of T cells to polarise under variousex vivoconditions.Methods:Purified CD4+T cells obtained from superantigen-treated mice were cultured under Thpolarising conditionsin vitro. By combining intracellular cytokine staining and subsequent flow cytometric analysis with quantitative cytokine measurements in culture supernatants by enzyme-linked immunosorbent assay (ELISA), the differential Thpolarising capacity of the treatment can be detected in a qualitative and quantitative manner.Results and conclusions:BALB/c mice were shown to be biased to develop strong Th2 polarised immune responses using Th0 stimulation of purified CD4+T cells from phosphate-buffered saline-treated mice. Nevertheless, our analysis methodology convincingly showed that even in these mice, Toxic Shock Syndrome Toxin-1 treatmentin vivoresulted in a significantly stronger Th1 polarising effect than control treatment. Our results indicate that populations of Thcells can be assessed individually for their differential Th1 or Th2 maturation capacityin vivoby analysing robustin vitropolarisation cultures combined with intracellular cytokine staining and ELISA.

scholarly journals Regulation of T Cell Responses by Ionic Salt Signals

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2365
Author(s):  
Christina E. Zielinski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Sodium Chloride ◽  
T Cell Responses ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Tissue Microenvironment ◽  
Cell Responses ◽  
The Impact

T helper cell responses are tailored to their respective antigens and adapted to their specific tissue microenvironment. While a great proportion of T cells acquire a resident identity, a significant proportion of T cells continue circulating, thus encountering changing microenvironmental signals during immune surveillance. One signal, which has previously been largely overlooked, is sodium chloride. It has been proposed to have potent effects on T cell responses in the context of autoimmune, allergic and infectious tissue inflammation in mouse models and humans. Sodium chloride is stringently regulated in the blood by the kidneys but displays differential deposition patterns in peripheral tissues. Sodium chloride accumulation might furthermore be regulated by dietary intake and thus by intentional behavior. Together, these results make sodium chloride an interesting but still controversial signal for immune modulation. Its downstream cellular activities represent a potential therapeutic target given its effects on T cell cytokine production. In this review article, we provide an overview and critical evaluation of the impact of this ionic signal on T helper cell polarization and T helper cell effector functions. In addition, the impact of sodium chloride from the tissue microenvironment is assessed for human health and disease and for its therapeutic potential.

scholarly journals IL-17+ Mast Cell/T Helper Cell Axis in the Early Stages of Acne

2021 ◽  
Vol 12 ◽  
Author(s):  
Yoan Eliasse ◽  
Edouard Leveque ◽  
Lucile Garidou ◽  
Louise Battut ◽  
Brienne McKenzie ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Immune Cell ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Cell Axis ◽  
Early Stages ◽  
Cutibacterium Acnes

Acne is a multifactorial disease driven by physiological changes occurring during puberty in the pilosebaceous unit (PSU) that leads to sebum overproduction and a dysbiosis involving notably Cutibacterium acnes. These changes in the PSU microenvironment lead to a shift from a homeostatic to an inflammatory state. Indeed, immunohistochemical analyses have revealed that inflammation and lymphocyte infiltration can be detected even in the infraclinical acneic stages, highlighting the importance of the early stages of the disease. In this study, we utilized a robust multi-pronged approach that included flow cytometry, confocal microscopy, and bioinformatics to comprehensively characterize the evolution of the infiltrating and resident immune cell populations in acneic lesions, beginning in the early stages of their development. Using a discovery cohort of 15 patients, we demonstrated that the composition of immune cell infiltrate is highly dynamic in nature, with the relative abundance of different cell types changing significantly as a function of clinical lesion stage. Within the stages examined, we identified a large population of CD69+ CD4+ T cells, several populations of activated antigen presenting cells, and activated mast cells producing IL-17. IL-17+ mast cells were preferentially located in CD4+ T cell rich areas and we showed that activated CD4+ T cells license mast cells to produce IL-17. Our study reveals that mast cells are the main IL-17 producers in the early stage of acne, underlying the importance of targeting the IL-17+ mast cell/T helper cell axis in therapeutic approaches.

scholarly journals The “one airway, one disease” concept in light of Th2 inflammation

2018 ◽  
Vol 52 (4) ◽  
pp. 1800437 ◽  
Author(s):  
Lisa Giovannini-Chami ◽  
Agnès Paquet ◽  
Céline Sanfiorenzo ◽  
Nicolas Pons ◽  
Julie Cazareth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Allergic Rhinitis ◽  
Bronchial Epithelium ◽  
T Helper Cell ◽  
Polymorphonuclear Neutrophils ◽  
Helper Cell ◽  
T Helper ◽  
Th2 Response ◽  
Large Variability ◽  
Th2 Inflammation

In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and bronchial cells were collected by brushing from healthy controls (C, n=13), patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry, gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell (Th17) and interferon (IFN) signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose excluded 30% of the initial cohort. All bronchial samples from the AR group were Th2-high. The gene expression profile of nasal samples from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2 response, in particular due to a more robust influence of the IFN response in 14 out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002), while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.

scholarly journals T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

Cell ◽  
2018 ◽  
Vol 175 (5) ◽  
pp. 1307-1320.e22 ◽  
Author(s):  
Moshe Biton ◽  
Adam L. Haber ◽  
Noga Rogel ◽  
Grace Burgin ◽  
Semir Beyaz ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Helper Cell ◽  
Intestinal Stem Cell ◽  
Helper Cell ◽  
Cell Renewal ◽  
T Helper ◽  
Stem Cell Renewal
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