scholarly journals AGE-RELATED ELEVATED CD4+ T HELPER 17 CELL RESPONSE PROMOTES PROSTATE CANCER CELL GROWTH, MIGRATION, AND INVASION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S879-S879
Author(s):  
Qiuyang Zhang ◽  
Sen Liu ◽  
Bing Zhang ◽  
Elizabeth Norton ◽  
S Michal Jazwinski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Th17 Cell ◽  
Aging Process ◽  
Conditioned Media ◽  
Migration And Invasion ◽  
T Helper ◽  
T Helper 17 ◽  
Age Related ◽  
Old Mice

Abstract Age is the most important risk factor for prostate cancer (PCa). But, how age contributes to PCa remains unknown. Interleukin-17 (IL-17) -producing CD4+ T helper 17 (Th17) cells play a critical role in inflammatory diseases. It is often elevated in aging humans and mice, however, whether aging affects Th17 cell function and subsequent PCa risk increase is unclear. In this study, we investigated the role of CD4+ T cells in PCa cell growth during the aging process. Splenic T cells were isolated and purified into CD4+CD25- T cells from young and old mice, then cultured in the presence of plate-bound anti-CD3/anti-CD28. Four days later, the cells were re-stimulated with PMA and ionomycin in the presence of brefeldin A for 4 hours and then were collected and used for flow cytometry and/or qPCR. The supernatant (conditioned media) from young and old cultures was collected and used in subsequent experiments. Flow and qPCR results showed that 17-producing T cells and associated cytokines were significantly increased in old mice compared to young mice. When PCa cell lines (LNCaP, DU-145, and PC3) were treated by the conditioned media for 48 and 72 hours. The cell proliferation, migration, and invasion, as well as the activation of NF-B signaling in PCa cells, were significantly increased after exposure to the conditioned media from aged mice, compared to that from young mice. These results indicated that age-related CD4+ Th17 cell responses are elevated in mice in the aging process and play an important role in PCa growth.

scholarly journals CD4 + T helper 17 cell response of aged mice promotes prostate cancer cell migration and invasion

The Prostate ◽  
2020 ◽  
Vol 80 (10) ◽  
pp. 764-776 ◽  
Author(s):  
Sen Liu ◽  
Fengli Liu ◽  
Bing Zhang ◽  
Peng Yan ◽  
Brian G. Rowan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Cell Response ◽  
Prostate Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cell

scholarly journals Pellino1 promotes chronic inflammatory skin disease via keratinocyte hyperproliferation and induction of the T helper 17 response

2020 ◽  
Vol 52 (9) ◽  
pp. 1537-1549
Author(s):  
Suhyeon Kim ◽  
Si-Yeon Lee ◽  
Seoyoon Bae ◽  
Jin-Kwan Lee ◽  
Kyungrim Hwang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Immune Responses ◽  
Th17 Cell ◽  
Skin Diseases ◽  
Psoriatic Skin ◽  
T Helper ◽  
T Helper 17 ◽  
Disease Manifestation ◽  
Inflammatory Skin

Abstract Psoriasis is one of the most common immune-mediated chronic inflammatory skin diseases. However, little is known about the molecular mechanism underlying the immunological circuits that maintain innate and adaptive immune responses in established psoriasis. In this study, we found that the Pellino1 (Peli1) ubiquitin E3 ligase is activated by innate pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs), and is highly upregulated in human psoriatic skin lesions and murine psoriasis-like models. Increased Peli1 expression is strongly correlated with the immunopathogenesis of psoriasis by activating hyperproliferation of keratinocytes in the S and G2/M phases of the cell cycle and promoting chronic skin inflammation. Furthermore, Peli1-induced psoriasis-like lesions showed significant changes in the expression levels of several T helper 17 (Th17)-related cytokines, such as IL-17a, IL-21, IL-22, IL-23, and IL-24, indicating that overexpression of Peli1 resulted in the sequential engagement of the Th17 cell response. However, the overexpression of Peli1 in T cells was insufficient to trigger psoriasis, while T cells were indispensable for disease manifestation. In summary, our findings demonstrate that Peli1 is a critical cell cycle activator of innate immunity, which subsequently links Th17 cell immune responses to the psoriatic microenvironment.

Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock

2015 ◽  
Vol 309 (3) ◽  
pp. G202-G208 ◽  
Author(s):  
Koji Morishita ◽  
Raul Coimbra ◽  
Simone Langness ◽  
Brian P. Eliceiri ◽  
Todd W. Costantini
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Response ◽  
Hemorrhagic Shock ◽  
Th17 Cell ◽  
Male Rats ◽  
T Helper ◽  
Mesenteric Lymph Nodes ◽  
T Helper 17 ◽  
Mesenteric Lymph

CD103+ dendritic cells (DCs) continuously migrate from the intestine to the mesenteric lymph nodes (MLNs) and maintain tolerance by driving the development of regulatory T cells (Treg) in the gut. The relative expression of Treg and T-helper 17 (Th17) cells determines the balance between tolerance and immunity in the gut. We hypothesized that trauma/hemorrhagic shock (T/HS) would decrease the CD103+ DC population in the mesenteric lymph and alter the Treg-to-Th17 ratio in the MLN. We further hypothesized that vagus nerve stimulation (VNS) would promote tolerance to inflammation by increasing the Treg-to-Th17 ratio in the MLN after injury. Male rats were assigned to sham shock (SS), trauma/sham shock (T/SS), or T/HS. T/HS was induced by laparotomy and 60 min of HS (blood pressure 35 mmHg) followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. MLN samples were collected 24 h after resuscitation. The CD103+ DC population and Treg-to-Th17 cell ratio in the MLN were decreased after T/HS compared with SS and T/SS, suggesting a shift to an inflammatory response. VNS prevented the T/HS-induced decrease in the CD103+ DC population and increased the Treg-to-Th17 ratio compared with T/HS alone. VNS alters the gut inflammatory response to injury by modulating the Treg-Th17 cell balance in the MLN. VNS promotes tolerance to inflammation in the gut, further supporting its ability to modulate the inflammatory set point and alter the response to injury.

scholarly journals Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

2021 ◽  
Vol 7 (21) ◽  
pp. eabe4601
Author(s):  
Sandro Da Mesquita ◽  
Jasmin Herz ◽  
Morgan Wall ◽  
Taitea Dykstra ◽  
Kalil Alves de Lima ◽  
...  
Keyword(s):  
T Cells ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Therapeutic Potential ◽  
T Cell Response ◽  
Age Related ◽  
Lymphatic Vasculature ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Old Mice

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

scholarly journals CD4+T Cells: Differentiation and Functions

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Rishi Vishal Luckheeram ◽  
Rui Zhou ◽  
Asha Devi Verma ◽  
Bing Xia
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Cytokine Signaling ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 17 ◽  
Differentiated Cells ◽  
Follicular Helper ◽  
Follicular Helper T Cell

CD4+T cells are crucial in achieving a regulated effective immune response to pathogens. Naive CD4+T cells are activated after interaction with antigen-MHC complex and differentiate into specific subtypes depending mainly on the cytokine milieu of the microenvironment. Besides the classical T-helper 1 and T-helper 2, other subsets have been identified, including T-helper 17, regulatory T cell, follicular helper T cell, and T-helper 9, each with a characteristic cytokine profile. For a particular phenotype to be differentiated, a set of cytokine signaling pathways coupled with activation of lineage-specific transcription factors and epigenetic modifications at appropriate genes are required. The effector functions of these cells are mediated by the cytokines secreted by the differentiated cells. This paper will focus on the cytokine-signaling and the network of transcription factors responsible for the differentiation of naive CD4+T cells.

scholarly journals Notch signaling pathway regulates CD4+CD25+CD127dim/− regulatory T cells and T helper 17 cells function in gastric cancer patients

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Lu Yang ◽  
Ke-Lei Zhao ◽  
Lei Qin ◽  
Dan-Xia Ji ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Notch Signaling ◽  
Cancer Progression ◽  
Th17 Cells ◽  
Cellular Proliferation ◽  
Current Data ◽  
T Helper ◽  
T Helper 17

Abstract Regulatory T cells (Tregs) and T helper 17 (Th17) cells contribute to cancer progression and prognosis. However, regulatory factors associated with Tregs–Th17 balance were not completely understood. We previously demonstrated an immune-modulatory capacity by Notch signaling inactivation to reverse Tregs–Th17 disequilibrium in chronic hepatitis C. Thus, the aim of current study was to assess the role of Notch signaling in modulation Tregs and Th17 cells function in gastric cancer (GC) patients. A total of 51 GC patients and 18 normal controls (NCs) were enrolled. Notch1 and Notch2 mRNA expressions were semiquantified by real-time polymerase chain reaction. Tregs/Th17 percentages, transcriptional factors, and cytokines production were investigated in response to the stimulation of Notch signaling inhibitor DAPT. Both Notch1 and Notch2 mRNA expressions were elevated in GC tissues and peripheral bloods in GC patients. CD4+CD25+CD127dim/− Tregs and Th17 cells percentage was also elevated in GC patients compared with in NCs. DAPT treatment did not affect frequency of either circulating Tregs or Th17 cells, however, reduced FoxP3/RORγt mRNA expression and interleukin (IL)-35/IL-17 production in purified CD4+ T cells from GC patients. Moreover, blockade of Notch signaling also inhibited the suppressive function of purified CD4+CD25+CD127dim/− Tregs from GC patients, which presented as elevation of cellular proliferation and IL-35 secretion. The current data further provided mechanism underlying Tregs–Th17 balance in GC patients. The link between Notch signaling and Th cells might lead to a new therapeutic target for GC patients.

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