scholarly journals TGFβ Suppresses Type 2 Immunity to Cancer

2020 ◽  
Author(s):  
Ming Liu ◽  
Fengshen Kuo ◽  
Kristelle J. Capistrano ◽  
Davina Kang ◽  
Briana G. Nixon ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Defense Mechanism ◽  
Transforming Growth Factor Β ◽  
Defense Strategies ◽  
Type 2 Immunity ◽  
Immunological Mechanisms

SummaryThe immune system employs two distinct defense strategies against infections: pathogen elimination typified by type 1 immunity, and pathogen containment exemplified by type 2 immunity in association with tissue repair. Akin to infectious diseases, cancer progresses with cancer cell acquisition of microorganism-like behavior propagating at the expense of the host. While immunological mechanisms of cancer cell elimination are well defined, whether immune-mediated cancer cell containment can be induced is poorly understood. Here we show that ablation of transforming growth factor-β receptor II (TGFβRII) in CD4+ T cells promotes tumor tissue healing and halts cancer progression. Notably, the restorative response is dependent on the T helper 2 cytokine IL-4 fortifying vasculature organization that spares only proximal layers of cancer cells from hypoxia, nutrient starvation and death. Thus, type 2 immunity represents an effective cancer defense mechanism, and TGFβ signaling in helper T cells may be targeted for novel cancer immunotherapy.

scholarly journals Interleukin-10- and Transforming Growth Factor β-Independent Regulation of CD8+T Cells Expressing Type 1 and Type 2 Cytokines in Human Lymphatic Filariasis

2014 ◽  
Vol 21 (12) ◽  
pp. 1620-1627 ◽  
Author(s):  
Rajamanickam Anuradha ◽  
Parakkal Jovvian George ◽  
Paul Kumaran ◽  
Thomas B. Nutman ◽  
Subash Babu
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Lymphatic Filariasis ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Transforming Growth Factor Β ◽  
Necrosis Factor Alpha ◽  
Type 2 Cytokines

ABSTRACTLymphatic filariasis is known to be associated with diminished CD4+Th1 and elevated CD4+Th2 responses to parasite-specific antigens. The roles of cytokine-expressing CD8+T cells in immune responses to filarial infections are not well defined. To study the roles of CD8+T cells expressing type 1, type 2, and type 17 cytokines in filarial infections, we examined the frequencies of these cells in clinically asymptomatic, patently infected (INF) individuals, directlyex vivoand in response to parasite or nonparasite antigens; these frequencies were compared with the results for individuals with filarial lymphedema (i.e., clinical pathology [CP]) and those without active infection or pathology (i.e., endemic normal [EN]). INF individuals exhibited significant decreases in the frequencies of CD8+T cells expressing tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin-22 (IL-22) at baseline and/or in response to filarial antigens, compared with CP and EN individuals. In contrast, the same individuals exhibited significant increases in the frequencies of CD8+T cells expressing IL-4, IL-5, IL-9, IL-13, and IL-21, compared with CP and/or EN individuals. Curative treatment resulted in significantly increased frequencies of CD8+T cells expressing IL-2 and significantly decreased frequencies of CD8+T cells expressing type 2 cytokines. Finally, the regulation of these responses appears to be independent of IL-10 and transforming growth factor β (TGF-β), since blockade of IL-10 or TGF-β signaling did not significantly alter the frequencies of type 1 or type 2 cytokine-expressing CD8+T cells. Our findings suggest that alterations in the frequencies of cytokine-expressing CD8+T cells are characteristic features of lymphatic filarial infections.

scholarly journals Suppression of Gamma Interferon Transcription and Production by Nematode Excretory-Secretory Antigen during Polyclonal Stimulation of Rat Lymph Node T Cells

2000 ◽  
Vol 68 (11) ◽  
pp. 6233-6239 ◽  
Author(s):  
Ryuichi Uchikawa ◽  
Shinji Matsuda ◽  
Naoki Arizono
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Cell Polarization ◽  
Gamma Interferon ◽  
Immunological Mechanisms ◽  
Ifn Γ

ABSTRACT Although certain helminth infections preferentially induce type 2 T-cell responses, the immunological mechanisms responsible for type 2 T-cell polarization remain unclear. In the present study, we investigated the effects of excretory-secretory (ES) antigen from the nematode Nippostrongylus brasiliensis on cytokine production by mesenteric lymph node (MLN) cells isolated from naive rats. MLN cells produced considerable levels of gamma interferon (IFN-γ) during a 72-h stimulation with concanavalin A (ConA) or with immobilized anti-CD3 plus soluble anti-CD28 antibodies (anti-CD3/CD28). With either stimulation, 10 μg of ES antigen per ml significantly suppressed IFN-γ and interleukin-2 (IL-2) production without cytotoxic activity. The copresence of anti-IL-4, anti-IL-10, or transforming growth factor β (TGF-β) blocking antibodies did not alter the suppressive effect of ES antigen on IFN-γ production. ES antigen did not affect IL-10 production. Kinetic studies of the effect of ES antigen indicated that the antigen suppressed even ongoing IFN-γ production. Reverse transcription-PCR study showed that in the presence of ES antigen, IFN-γ mRNA expression by MLN cells was suppressed 6 and 12 h after ConA or anti-CD3/CD28 stimulation. ES antigen also significantly suppressed IFN-γ production by purified CD4+ or CD8+ T cells during anti-CD3/CD28 stimulation but did not affect IL-4 production by CD4+ T cells. These findings suggested that the nematode antigen suppressed production of IFN-γ and IL-2 but not IL-4 or IL-10 production. ES antigen-mediated suppression of IFN-γ during the initiation of the immune response may provide a microenvironment that helps generation of type 2 T cells.

Expression of CD4+CD25+Foxp3+ Regulatory T Cells, Interleukin 10 and Transforming Growth Factor β in Newly Diagnosed Type 2 Diabetic Patients

2017 ◽  
Vol 126 (02) ◽  
pp. 96-101 ◽  
Author(s):  
Ning Yuan ◽  
Hai-feng Zhang ◽  
Qi Wei ◽  
Ping Wang ◽  
Wei-ying Guo
Keyword(s):  
Insulin Resistance ◽  
T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Obese Group ◽  
Control Group ◽  
Newly Diagnosed ◽  
Significant Difference

Abstract Background Recent studies have shown that dysfunction and decrease of regulatory T cells (Tregs) correlates with insulin resistance (IR), one of the most significant mechanisms for type 2 diabetes mellitus (T2DM). To examine potential relationships among Tregs, IR, blood lipid content, and related cytokines, we investigated the frequency of CD4+CD25+Foxp3+ Tregs, as well as expression levels of interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) in newly diagnosed T2DM patients. Methods Fifty-one newly diagnosed T2DM patients and 55 control individuals were enrolled. According to body mass index (BMI), the T2DM patients were grouped into non-obese and obese groups. Blood was collected in ethylene diamine tetraacetic acid (EDTA) anticoagulant tubes for detection of CD4+CD25+Foxp3+ Tregs by flow cytometry. Serum was collected to quantify IL-10 and TGF-β levels by enzyme-linked immunosorbent assay (ELISA). By comparing percentages of Tregs between non-obese and obese groups, correlation with Treg frequency, homeostasis model assessment of insulin resistance (HOMA-IR), IL-10 and TGF-β was examined. Results The percentage of CD4+CD25+Foxp3+ Tregs in the newly diagnosed T2DM group was significantly lower than in the control group (P<0.01). Further, levels of IL-10 and TGF-β were also lower in the T2DM group (P<0.05). The level of IL-10 was remarkably lower in the obese group than in the non-obese and the control groups (P<0.01), but there was no significant difference between non-obese group and the control group. The level of TGF-β was lower in obese group than in the control group (P<0.05). There was no significant difference between non-obese group and the control group. The frequency of CD4+CD25+Foxp3+ Tregs in the obese group was significantly lower than in the non-obese group (P<0.05). In the obese group, the percentage of Tregs negatively correlated with HOMA-IR and positively correlated with TGF-β (P<0.05). There was no obvious correlation between Treg and HOMA-IR in the non-obese group. Conclusion The percentage of CD4+CD25+Foxp3+ Tregs and levels of related cytokines IL-10 and TGF-β were precipitously decreased in newly diagnosed T2DM patients. Therefore, the function of Tregs in limiting the proinflammatory milieu represents an important pathogenic mediator of the development of obesity-induced IR in newly diagnosed T2DM patients. Notably, TGF-β may play an important role in this process. Thus, enhancing expression of Tregs may improve IR in newly diagnosed T2DM patients with obesity.

scholarly journals Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 336
Author(s):  
Roberta Melchionna ◽  
Paola Trono ◽  
Annalisa Tocci ◽  
Paola Nisticò
Keyword(s):  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Homeostasis ◽  
Actin Dynamics ◽  
Human Tissues ◽  
Cellular Functions ◽  
Tgfβ Signaling ◽  
Physical Mechanisms ◽  
And Function

Human tissues, to maintain their architecture and function, respond to injuries by activating intricate biochemical and physical mechanisms that regulates intercellular communication crucial in maintaining tissue homeostasis. Coordination of the communication occurs through the activity of different actin cytoskeletal regulators, physically connected to extracellular matrix through integrins, generating a platform of biochemical and biomechanical signaling that is deregulated in cancer. Among the major pathways, a controller of cellular functions is the cytokine transforming growth factor β (TGFβ), which remains a complex and central signaling network still to be interpreted and explained in cancer progression. Here, we discuss the link between actin dynamics and TGFβ signaling with the aim of exploring their aberrant interaction in cancer.

scholarly journals Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1084
Author(s):  
Junya Ono ◽  
Masayuki Takai ◽  
Ayami Kamei ◽  
Yoshinori Azuma ◽  
Kenji Izuhara
Keyword(s):  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Biological Fluids ◽  
Allergic Inflammation ◽  
Transforming Growth Factor Β ◽  
Serum Levels ◽  
Vital Role ◽  
Interleukin 4 ◽  
Type 2 Inflammation

Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management of type 2 inflammation and fibrotic diseases since heterogeneity is of utmost importance. Periostin expression is induced by type 2 cytokines (interleukin-4/-13) or transforming growth factor-β, and plays a vital role in the pathogenesis of allergic inflammation or interstitial lung disease, respectively, andits serum levels are correlated disease severity, prognosis and responsiveness to the treatment. We first summarise the importance of type 2 biomarker and then describe the pathological role of periostin in the development and progression of type 2 allergic inflammation and pulmonary fibrosis. In addition, then, we summarise the recent development of assay methods for periostin detection, and analyse the diseases in which periostin concentration is elevated in serum and local biological fluids and its usefulness as a biomarker. Furthermore, we describe recent findings of periostin as a biomarker in the use of biologics or anti-fibrotic therapy. Finally, we describe the factors that influence the change in periostin concentration under the healthy conditions.

scholarly journals Tumor Immune Evasion Induced by Dysregulation of Erythroid Progenitor Cells Development

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 870
Author(s):  
Tomasz M. Grzywa ◽  
Magdalena Justyniarska ◽  
Dominika Nowis ◽  
Jakub Golab
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Progenitor Cells ◽  
Cancer Progression ◽  
Immune Evasion ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Interleukin 10 ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

Cancer cells harness normal cells to facilitate tumor growth and metastasis. Within this complex network of interactions, the establishment and maintenance of immune evasion mechanisms are crucial for cancer progression. The escape from the immune surveillance results from multiple independent mechanisms. Recent studies revealed that besides well-described myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) or regulatory T-cells (Tregs), erythroid progenitor cells (EPCs) play an important role in the regulation of immune response and tumor progression. EPCs are immature erythroid cells that differentiate into oxygen-transporting red blood cells. They expand in the extramedullary sites, including the spleen, as well as infiltrate tumors. EPCs in cancer produce reactive oxygen species (ROS), transforming growth factor β (TGF-β), interleukin-10 (IL-10) and express programmed death-ligand 1 (PD-L1) and potently suppress T-cells. Thus, EPCs regulate antitumor, antiviral, and antimicrobial immunity, leading to immune suppression. Moreover, EPCs promote tumor growth by the secretion of growth factors, including artemin. The expansion of EPCs in cancer is an effect of the dysregulation of erythropoiesis, leading to the differentiation arrest and enrichment of early-stage EPCs. Therefore, anemia treatment, targeting ineffective erythropoiesis, and the promotion of EPC differentiation are promising strategies to reduce cancer-induced immunosuppression and the tumor-promoting effects of EPCs.

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