scholarly journals Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2758 ◽  
Author(s):  
Yin-Hua Cheng ◽  
Ih-Sheng Chen ◽  
Ying-Chi Lin ◽  
Chun-Wei Tung ◽  
Hsun-Shuo Chang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Caryophyllene Oxide ◽  
Immune Disorders ◽  
T Helper ◽  
T Helper 1 ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Background T cells play a pivotal role in the adaptive immunity that participates in a wide range of immune responses through a complicated cytokine network. Imbalance of T-cell responses is involved in several immune disorders. Neolitsea species, one of the biggest genera in the family Lauraceae, have been employed widely as folk medicines for a long time in Asia. Previous phytochemical investigations revealed the abundance of terpenes in the leaves of N. hiiranensis, an endemic Neolitsea in Taiwan, and demonstrated anti-inflammatory activities. However, the effect of N. hiiranensis on the functionality of immune cells, especially T cells, is still unclear. In this study, we utilize in vitro and in vivo approaches to characterize the effects of leaves of N. hiiranensis and its terpenoids on adaptive immune responses. Methods Dried leaves of N. hiiranensis were extracted three times with cold methanol to prepare crude extracts and to isolate its secondary metabolites. The ovalbumin (OVA)-sensitized BALB/c mice were administrated with N. hiiranensis extracts (5–20 mg/kg). The serum and splenocytes of treated mice were collected to evaluate the immunomodulatory effects of N. hiiranensis on the production of OVA-specific antibodies and cytokines. To further identify the N. hiiranensis-derived compounds with immunomodulatory potentials, OVA-primed splenocytes were treated with compounds isolated from N. hiiranensis by determining the cell viability, cytokine productions, and mRNA expression in the presence of OVA in vitro. Results Crude extracts of leaves of N. hiiranensis significantly inhibited IL-12, IFN-γ, and IL-2 cytokine productions as well as the serum levels of antigen-specific IgM and IgG2a in vivo. Two of fourteen selected terpenoids and one diterpenoid derived from the leaves of N. hiiranensis suppressed IFN-γ in vitro. In addition, β-caryophyllene oxide attenuated the expression of IFN-γ, T-bet, and IL-12Rβ2 in a dose-dependent manner. N. hiiranensis-derived β-caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN-γ production, and Th1-assocaited genes. Conclusion As IFN-γ is the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that the N. hiiranensis and its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.

scholarly journals CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo

2003 ◽  
Vol 198 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Guillaume Oldenhove ◽  
Magali de Heusch ◽  
Georgette Urbain-Vansanten ◽  
Jacques Urbain ◽  
Charlie Maliszewski ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Peripheral Tolerance ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon γ–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.

scholarly journals Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions

2009 ◽  
Vol 206 (13) ◽  
pp. 3101-3114 ◽  
Author(s):  
Olga Schulz ◽  
Elin Jaensson ◽  
Emma K. Persson ◽  
Xiaosun Liu ◽  
Tim Worbs ◽  
...  
Keyword(s):  
Immune Responses ◽  
Direct Injection ◽  
Turnover Rates ◽  
Mesenteric Lymph Nodes ◽  
Adaptive Immune Responses ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Inflammatory Conditions

Chemokine receptor CX3CR1+ dendritic cells (DCs) have been suggested to sample intestinal antigens by extending transepithelial dendrites into the gut lumen. Other studies identified CD103+ DCs in the mucosa, which, through their ability to synthesize retinoic acid (RA), appear to be capable of generating typical signatures of intestinal adaptive immune responses. We report that CD103 and CX3CR1 phenotypically and functionally characterize distinct subsets of lamina propria cells. In contrast to CD103+ DC, CX3CR1+ cells represent a nonmigratory gut-resident population with slow turnover rates and poor responses to FLT-3L and granulocyte/macrophage colony-stimulating factor. Direct visualization of cells in lymph vessels and flow cytometry of mouse intestinal lymph revealed that CD103+ DCs, but not CX3CR1-expressing cells, migrate into the gut draining mesenteric lymph nodes (LNs) under steady-state and inflammatory conditions. Moreover, CX3CR1+ cells displayed poor T cell stimulatory capacity in vitro and in vivo after direct injection of cells into intestinal lymphatics and appeared to be less efficient at generating RA compared with CD103+ DC. These findings indicate that selectively CD103+ DCs serve classical DC functions and initiate adaptive immune responses in local LNs, whereas CX3CR1+ populations might modulate immune responses directly in the mucosa and serve as first line barrier against invading enteropathogens.

scholarly journals The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1021
Author(s):  
Ho-Jae Lee ◽  
Joon Seok Park ◽  
Hyun Jung Yoo ◽  
Hae Min Lee ◽  
Byung Cheon Lee ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Methionine Sulfoxide Reductase ◽  
Interleukin 12 ◽  
T Helper ◽  
T Helper 1

Immune activation associates with the intracellular generation of reactive oxygen species (ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidence shows that ROS-mediated signal transduction can be regulated by selenoproteins such as methionine sulfoxide reductase B1 (MsrB1). However, how the selenoprotein shapes immunity remains poorly understood. Here, we demonstrated that MsrB1 plays a crucial role in the ability of dendritic cells (DCs) to provide the antigen presentation and costimulation that are needed for cluster of differentiation antigen four (CD4) T-cell priming in mice. We found that MsrB1 regulated signal transducer and activator of transcription-6 (STAT6) phosphorylation in DCs. Moreover, both in vitro and in vivo, MsrB1 potentiated the lipopolysaccharide (LPS)-induced Interleukin-12 (IL-12) production by DCs and drove T-helper 1 (Th1) differentiation after immunization. We propose that MsrB1 activates the STAT6 pathway in DCs, thereby inducing the DC maturation and IL-12 production that promotes Th1 differentiation. Additionally, we showed that MsrB1 promoted follicular helper T-cell (Tfh) differentiation when mice were immunized with sheep red blood cells. This study unveils as yet unappreciated roles of the MsrB1 selenoprotein in the innate control of adaptive immunity. Targeting MsrB1 may have therapeutic potential in terms of controlling immune reactions.

scholarly journals Undaria pinnatifida Fucoidan-Rich Extract Induces Both Innate and Adaptive Immune Responses

2019 ◽  
Vol 14 (8) ◽  
pp. 1934578X1987372
Author(s):  
Hwan H. Lee ◽  
Yoo J. Cho ◽  
Daeung Yu ◽  
Donghwa Chung ◽  
Gun-Hee Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cd8 T Cells ◽  
Undaria Pinnatifida ◽  
Plasma Concentrations ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Tnf Α ◽  
Ifn Γ

Fucoidans are widely used as an ingredient of dietary supplements. We investigated the immune stimulatory activities of Undaria pinnatifida ( Alariaceae) fucoidan-rich extract (UPF-RE) in vitro as well as in vivo . In vitro, the extract stimulated Raw 264.7 cells to produce significant nitric oxide (NO) metabolites and cytokines (TNF-α, IL-1α, IL-1β, and IL-6). It also induced the proliferation of primary mouse splenocytes and the secretion of IL-4, which correlated with the phosphorylation of Extracellular-signal-regulated kinase (ERK) protein. In in vivo experiments, first, 50 mg/kg of 3 different types of UPF-RE, DSU02, DSU02L (low molecular weight, <3 kDa), and DSU02H (high molecular weight, >10 kDa), were orally administered to C57BL/6 mice. After 14 days, the frequencies of CD3+, CD4+, and CD8+ T cells and NK cells from each group were analyzed. Plasma concentrations of TNF-α and IFN-γ were determined. The frequencies of CD3+ and CD4+ showed a statistically significant increase in splenocytes isolated from the DSU02 and DSU02H groups. Also, there was significant production of TNF-α and IFN-γ from the DSU02 group. Second, 3 different concentrations of DSU02 (50, 100, and 150 mg/kg) were orally administered. After 14 days, the proliferative capacity of CD3+, CD4+, and CD8+ T cells was investigated, and the plasma concentrations of IgM and total IgG were determined. Plasma concentration of IgM from the DSU02 150 mg/kg group was statistically significantly higher compared with that from the other groups. We suggest that UPF-RE could be a good candidate for a natural immune stimulator to induce innate as well as adaptive immune responses.

scholarly journals Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

2020 ◽  
Author(s):  
Kuai Yu ◽  
Yongjian Wu ◽  
Jingjing He ◽  
Xuefei Liu ◽  
Bo Wei ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Adaptive Immune Responses ◽  
Activated T Cells ◽  
T Effector Cells ◽  
Adaptive Immune ◽  
The Impact ◽  
Excessive Activation

Abstract Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed a distinct feature of adaptive immunity in severely affected patients, the coincidence of impaired cellular and enhanced humoral immune responses, suggesting that dysregulated adaptive immune responses advanced severe COVID-19. Excessive activation and exhaustion were observed in CD8 T effector cells, which might contribute to the lymphopenia. Interestingly, expression of Prothymosin alpha (PTMA), the proprotein of Tα1, was significantly increased in a group of CD8 T memory stem cells, but not in excessively activated T cells. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

scholarly journals Protein Kinase C θ Is Critical for the Development of In Vivo T Helper (Th)2 Cell But Not Th1 Cell Responses

2004 ◽  
Vol 200 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Benjamin J. Marsland ◽  
Timothy J. Soos ◽  
Gerald Späth ◽  
Dan R. Littman ◽  
Manfred Kopf
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Immune Responses ◽  
T Helper ◽  
Antigen Concentration ◽  
Kinase C ◽  
Th2 Development

The serine/threonine-specific protein kinase C (PKC)-θ is predominantly expressed in T cells and localizes to the center of the immunological synapse upon T cell receptor (TCR) and CD28 signaling. T cells deficient in PKC-θ exhibit reduced interleukin (IL)-2 production and proliferative responses in vitro, however, its significance in vivo remains unclear. We found that pkc-θ−/− mice were protected from pulmonary allergic hypersensitivity responses such as airway hyperresponsiveness, eosinophilia, and immunoglobulin E production to inhaled allergen. Furthermore, T helper (Th)2 cell immune responses against Nippostrongylus brasiliensis were severely impaired in pkc-θ−/− mice. In striking contrast, pkc-θ−/− mice on both the C57BL/6 background and the normally susceptible BALB/c background mounted protective Th1 immune responses and were resistant against infection with Leishmania major. Using in vitro TCR transgenic T cell–dendritic cell coculture systems and antigen concentration-dependent Th polarization, PKC-θ–deficient T cells were found to differentiate into Th1 cells after activation with high concentrations of specific peptide, but to have compromised Th2 development at low antigen concentration. The addition of IL-2 partially reconstituted Th2 development in pkc-θ−/− T cells, consistent with an important role for this cytokine in Th2 polarization. Taken together, our results reveal a central role for PKC-θ signaling during Th2 responses.

scholarly journals Nociceptin/Orphanin FQ Suppresses Adaptive Immune Responses In Vivo and at Picomolar Levels In Vitro

2010 ◽  
Vol 5 (1) ◽  
pp. 143-154 ◽  
Author(s):  
Benito Anton ◽  
Phillipe Leff ◽  
Joseph J. Meissler ◽  
Juan C. Calva ◽  
Rodolfo Acevedo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Orphanin Fq ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

2020 ◽  
Author(s):  
Kuai Yu ◽  
Yongjian Wu ◽  
Jingjing He ◽  
Xuefei Liu ◽  
Bo Wei ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Severe Disease ◽  
Adaptive Immune Responses ◽  
Activated T Cells ◽  
Adaptive Immune ◽  
The Impact ◽  
Excessive Activation

Abstract Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed dysregulated adaptive immune responses in patients with severe disease. A new cluster of excessively activated CD8 T cells (Tea) was further identified, which displayed exhausted phenotypes and diminished function of antigen recognition. Interestingly, expression of PTMA, the proprotein of Tα1, was significantly increased in a group of highly proliferating CD8 T cells with memory stem cell features. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

scholarly journals Human‐engineered Treg‐like cells suppress FOXP3‐deficient T cells but preserve adaptive immune responses in vivo

2020 ◽  
Vol 9 (11) ◽  
Author(s):  
Yohei Sato ◽  
Laura Passerini ◽  
Brian D Piening ◽  
Molly Javier Uyeda ◽  
Marianne Goodwin ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals Reprogramming immune responses via microRNA modulation

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Juan R. Cubillos-Ruiz ◽  
Melanie R Rutkowski ◽  
Julia Tchou ◽  
Jose R. Conejo-Garcia
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Interventions ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Recent Advances ◽  
Individual Mirnas ◽  
Selective Modulation

AbstractIt is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miRNAs, both in vitro and in vivo. Here, we summarize recent advances in our understanding of how miRNAs drive the activity of immune cells, and how their modulation in vivo opens new avenues for diagnostic and therapeutic interventions in multiple diseases, from immunodeficiency to cancer. Recent contributions from our laboratory and other groups to novel formulations for miRNA mimetics are further discussed

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