scholarly journals Mast Cell-Derived Exosomes Promote Th2 Cell Differentiation via OX40L-OX40 Ligation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fei Li ◽  
Yuping Wang ◽  
Lihui Lin ◽  
Juan Wang ◽  
Hui Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Cell Types ◽  
Th2 Cells ◽  
Contact Method ◽  
Th2 Cell ◽  
Proliferation And Differentiation ◽  
Direct Cell ◽  
Different Cell Types ◽  
Different Origin

Exosomes are nanovesicles released by different cell types, such as dendritic cells (DCs), mast cells (MCs), and tumor cells. Exosomes of different origin play a role in antigen presentation and modulation of immune response to infectious disease. In this study, we demonstrate that mast cells and CD4+T cells colocated in peritoneal lymph nodes from BALB/c mouse. Further, bone marrow-derived mast cells (BMMCs) constitutively release exosomes, which express CD63 and OX40L. BMMC-exosomes partially promoted the proliferation of CD4+T cells. BMMC-exosomes significantly enhanced the differentiation of naive CD4+T cells to Th2 cells in a surface contact method, and this ability was partly inhibited by the addition of anti-OX40L Ab. In conclusion, BMMC-exosomes promoted the proliferation and differentiation of Th2 cells via ligation of OX40L and OX40 between exosomes and T cells. This method represents a novel mechanism, in addition to direct cell surface contacts, soluble mediators, and synapses, to regulate T cell actions by BMMC-exosomes.

scholarly journals Biology and Clinical Applicability of Plasma Thymus and Activation-Regulated Chemokine (TARC) in Classical Hodgkin Lymphoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 884
Author(s):  
Eline A. M. Zijtregtop ◽  
Iris van der Strate ◽  
Auke Beishuizen ◽  
Christian M. Zwaan ◽  
Marijn A. Scheijde-Vermeulen ◽  
...  
Keyword(s):  
T Cells ◽  
Hodgkin Lymphoma ◽  
Cell Types ◽  
Th2 Cells ◽  
Classical Hodgkin Lymphoma ◽  
Th2 Cell ◽  
Clinical Applicability ◽  
Antagonists And Inhibitors ◽  
Different Cell Types

Thymus and activation-regulated chemokine (TARC) is produced by different cell types and is highly expressed in the thymus. It plays an important role in T cell development, trafficking and activation of mature T cells after binding to its receptor C-C chemokine receptor type 4 (CCR4) and consecutive signal transducer and activator of transcription 6 (STAT6) activation. Importantly, TARC is also produced by malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). In cHL, HRS cells survive and proliferate due to the micro-environment consisting primarily of type 2 T helper (Th2) cells. TARC-mediated signaling initiates a positive feedback loop that is crucial for the interaction between HRS and T cells. The clinical applicability of TARC is diverse. It is useful as diagnostic biomarker in both children and adults with cHL and in other Th2-driven diseases. In adult cHL patients, TARC is also a biomarker for treatment response and prognosis. Finally, blocking TARC signaling and thus inhibiting pathological Th2 cell recruitment could be a therapeutic strategy in cHL. In this review, we summarize the biological functions of TARC and focus on its role in cHL pathogenesis and as a biomarker for cHL and other diseases. We conclude by giving an outlook on putative therapeutic applications of antagonists and inhibitors of TARC-mediated signaling.

scholarly journals Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.

1996 ◽  
Vol 184 (2) ◽  
pp. 473-483 ◽  
Author(s):  
T Sornasse ◽  
P V Larenas ◽  
K A Davis ◽  
J E de Vries ◽  
H Yssel
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Th2 Cells ◽  
Cell Phenotype ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th1 And Th2

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.

scholarly journals Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Simon Schreiber ◽  
Christoph M. Hammers ◽  
Achim J. Kaasch ◽  
Burkhart Schraven ◽  
Anne Dudeck ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Allergic Diseases ◽  
Building Blocks ◽  
Th2 Cells ◽  
Th Cells ◽  
Th2 Cell ◽  
Type 2 Immunity ◽  
Mediate Immunity

The function of T cells is critically dependent on their ability to generate metabolic building blocks to fulfil energy demands for proliferation and consecutive differentiation into various T helper (Th) cells. Th cells then have to adapt their metabolism to specific microenvironments within different organs during physiological and pathological immune responses. In this context, Th2 cells mediate immunity to parasites and are involved in the pathogenesis of allergic diseases including asthma, while CD8+ T cells and Th1 cells mediate immunity to viruses and tumors. Importantly, recent studies have investigated the metabolism of Th2 cells in more detail, while others have studied the influence of Th2 cell-mediated type 2 immunity on the tumor microenvironment (TME) and on tumor progression. We here review recent findings on the metabolism of Th2 cells and discuss how Th2 cells contribute to antitumor immunity. Combining the evidence from both types of studies, we provide here for the first time a perspective on how the energy metabolism of Th2 cells and the TME interact. Finally, we elaborate how a more detailed understanding of the unique metabolic interdependency between Th2 cells and the TME could reveal novel avenues for the development of immunotherapies in treating cancer.

Co-activation of naive CD4+ T cells and bone marrow-derived mast cells results in the development of Th2 cells

1995 ◽  
Vol 7 (4) ◽  
pp. 525-532 ◽  
Author(s):  
Christoph Huels ◽  
Tieno Germann ◽  
Sigrid Goedert ◽  
Petra Hoehn ◽  
Stephan Koelsch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Mast Cells ◽  
Cd4 T Cells ◽  
Th2 Cells ◽  
Co Activation

scholarly journals T-cell–intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy

2016 ◽  
Vol 113 (5) ◽  
pp. E568-E576 ◽  
Author(s):  
Jimena Perez-Lloret ◽  
Isobel S. Okoye ◽  
Riccardo Guidi ◽  
Yashaswini Kannan ◽  
Stephanie M. Coomes ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Allergic Diseases ◽  
Treg Cells ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Cytokines And Chemokines ◽  
Th2 Cell

There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αβ+CD4+ T-helper 2 (TH2) cells orchestrate the type-2–driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic TH2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic TH cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081–E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1α)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4gfp+αβ+CD4+ TH2 cells but not in TH1, TH17, or Treg cells. Testing this prediction, we restricted Trim24 deficiency to T cells by using a mixed bone marrow chimera system and found that T-cell–intrinsic Trim24 is essential for HDM-mediated airway allergy and antihelminth immunity. Mechanistically, HDM-elicited Trim24−/− T cells have reduced expression of many TH2 cytokines and chemokines and were predicted to have compromised IL-1–regulated signaling. Following this prediction, we found that Trim24−/− T cells have reduced IL-1 receptor (IL-1R) expression, are refractory to IL-1β–mediated activation in vitro and in vivo, and fail to respond to IL-1β–exacerbated airway allergy. Collectively, these data identify a previously unappreciated Trim24-dependent requirement for IL-1R expression on TH2 cells and an important nonredundant role for T-cell–intrinsic Trim24 in TH2-mediated allergy and antihelminth immunity.

Growth and differentiation factors in tracheobronchial epithelium

1991 ◽  
Vol 260 (6) ◽  
pp. L361-L373 ◽  
Author(s):  
A. M. Jetten
Keyword(s):  
Normal Structure ◽  
Cell Types ◽  
Regulatory Factors ◽  
Biochemical Processes ◽  
Polypeptide Growth Factors ◽  
Tracheobronchial Epithelium ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Population Interactions ◽  
Different Cell Types

The normal tracheobronchial epithelium is continuously renewing itself: cells are lost and replaced by the proliferation and differentiation of stem cells. The proliferation and differentiation of these cells have to be tightly controlled in order to maintain the normal structure of the epithelium. A variety of biological and biochemical processes are involved in controlling the proliferation and differentiation of the tracheobronchial epithelium. Since the trachea and bronchus are comprised of a heterogeneous cell population, interactions between the different cell types are of crucial importance not only in controlling the normal maintenance of this tissue but also in the regulation of repair processes following injury and morphogenesis during lung development. A variety of factors, including several polypeptide growth factors and cytokines, have been identified that regulate positively or negatively the growth and differentiation of tracheobronchial epithelial cells by autocrine or paracrine mechanisms. Retinoids are another group of regulatory factors that appear to play a crucial role in controlling cell proliferation and differentiation in the tracheobronchial epithelium. Recently, many advances have been made in understanding the action of these agents in these cells. Alterations in the balance between growth and differentiation regulatory factors appear to play an important role in several pathophysiological changes such as hyperplasia, fibrosis, and neoplasia.

scholarly journals Downregulation of miRNA-451a Promotes the Differentiation of CD4+ T Cells towards Th2 Cells by Upregulating ETS1 in Childhood Asthma

2020 ◽  
pp. 1-11
Author(s):  
Tianyue  Wang ◽  
Qianlan Zhou ◽  
Yunxiao Shang
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Peripheral Blood Lymphocytes ◽  
Cell Polarization ◽  
Luciferase Assay ◽  
Th2 Cells ◽  
Th2 Cell ◽  
Novel Target

Children exposed to common aeroallergens may develop asthma that progresses into adulthood. Inflammation regulated by T helper 2 (Th2) cells, a specific subpopulation of CD4+ T lymphocytes, is involved in asthmatic injury. Herein, our microarray data indicated that microRNA-451a-5p (miRNA-451a) expression decreased by 4.6-fold and ETS proto-oncogene 1 (ETS1) increased by 2.2-fold in the peripheral blood lymphocytes isolated from asthmatic children (<i>n</i> = 4) as compared to control individuals (<i>n</i> = 4). The negative correlation between miRNA-451a and ETS1 was further validated in 40 CD4+ T cell samples (10 healthy vs. 30 asthmatic samples). In vitro, naïve CD4+ T cells isolated from control individuals were cultured under Th2 cell polarizing condition. miRNA-451a expression decreased while ETS1 increased in CD4+ T cells in the setting of Th2 cell polarization. Moreover, miRNA-451a knockdown enhanced Th2 cell polarization – cells positive for both GATA3 (GATA binding protein 3, a Th2-transcription factor) and CD4 increased, and the generation of Th2 cell cytokines, interleukin (IL)5 and IL13, increased. In contrast, miRNA-451a overexpression inhibited Th2 cell differentiation. Interestingly, dual-Luciferase assay proved ETS1 as a novel target of miRNA-451a. Moreover, enforced expression of ETS1 partially restored miRNA-451a-induced inhibition of IL5 and IL13, and increased the GATA3+CD4+ cell population. Collectively, our work demonstrates that downregulation of miRNA-451a upregulates ETS1 expression in CD4+ T cells, which may contribute to Th2 cell differentiation in pediatric asthma.

scholarly journals Tumor Rejection by Disturbing Tumor Stroma Cell Interactions

2001 ◽  
Vol 194 (11) ◽  
pp. 1549-1560 ◽  
Author(s):  
Sabrina Ibe ◽  
Zhihai Qin ◽  
Thomas Schüler ◽  
Susanne Preiss ◽  
Thomas Blankenstein
Keyword(s):  
T Cells ◽  
Tumor Stroma ◽  
Residual Tumor ◽  
Cell Types ◽  
Cell Interactions ◽  
Tumor Rejection ◽  
Receptor Expression ◽  
Stroma Cell ◽  
Ifn Γ ◽  
Different Cell Types

The stroma of solid tumors is a complex network of different cell types. We analyzed stroma cell interactions in two tumor models during cyclophosphamide (Cy)-induced tumor rejection. In growing tumors, tumor infiltrating macrophages (TIMs) produced interleukin (IL)-10. Beginning 6 h after Cy-treatment T cells in the tumor were inactivated and TIMs switched to interferon (IFN)-γ production. Both, IL-10 production before and IFN-γ production after Cy-treatment by TIMs required T cells. With the same kinetics as TIMs started to produce IFN-γ the tumor vasculature was destroyed which required IFN-γ receptor expression on host but not tumor cells. These events preceded hemorrhagic necrosis and residual tumor cell elimination by T cells. Together, T cells regulate the function of TIMs and tumor rejection can be induced by disturbing the stroma network.

scholarly journals Single-cell RNA-Seq Reveals Transcriptional Landscape and Intra-tumor Heterogenicity in Gallbladder Cancer Liver Metastasis Microenvironment

2020 ◽  
Author(s):  
Wenhua You ◽  
Xiangyu Li ◽  
Peng Wang ◽  
Bowen Sha ◽  
Yuan Liang ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Metastasis ◽  
Gallbladder Cancer ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Malignant Cells ◽  
Different Cell Types ◽  
High Degree

Abstract Background: Gallbladder cancer (GBC) is a highly aggressive biliary epithelial malignancy. Tumor invasion and metastasis contributed to the high mortality of GBC patients. However, molecular mechanisms involved in GBC metastases are still little known. Methods: We performed single-cell RNA sequencing on GBC liver metastasis tissue and analyzed the data based on different cell types.Results: In this study, 8 cell types, including T cells, B cells, malignant cells, fibroblasts, endothelial cells, macrophages, dendritic cells, and mast cells were identified. Malignant cells displayed a high degree of intra-tumor heterogenicity and neutrophils could promote GBC progression in vitro. Besides, cytotoxic CD8+ T cells became exhausted and CD4+ Tregs presented immunosuppressive characteristics. Macrophages played an important role in the tumor microenvironment. We identified three distinct macrophage subsets and emerged M2 polarization. We also found that cancer-associated fibroblasts exhibited heterogeneity and promoted GBC metastasis. Conclusions: In conclusion, our work provided a landscape view at the single-cell level and may clear the way for the therapy of GBC metastases.

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