scholarly journals Combination with Methotrexate and Cyclophosphamide Attenuated Maturation of Dendritic Cells: Inducing Treg Skewing and Th17 SuppressionIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoyang Yu ◽  
Caihong Wang ◽  
Jing Luo ◽  
Xiangcong Zhao ◽  
Lixing Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Helper ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Treatment ◽  
Immune Disorder ◽  
Key Factor ◽  
Antigen Presenting ◽  
Normal Immune Response ◽  
Dc Maturation

Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4+T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy. In this study, we investigated the effect of MTX and CTX on DC maturation in ovalbumin (OVA) immunized mice. Th17 inflammatory response is stronger, while the level of DCs maturity is higher. In contrast, the immunosuppression of Treg is stronger. We found that MTX combined with CTX significantly inhibited the DCs maturity and downregulated the antigen presenting capacity of DCs. As a result, it reestablished a balance of Th17 and Treg. Our study adds a novel mechanism and therapeutic target of MTX combined with CTX for autoimmune disease treatment.

scholarly journals Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Tumor Bed ◽  
Distinct Lineage ◽  
Human Dendritic Cells ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

scholarly journals Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Transplant Recipients ◽  
T Helper ◽  
T Helper 2 ◽  
Immature Dendritic Cells ◽  
And Migration ◽  
Mixed Lymphocyte Reactions ◽  
Dc Maturation

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.

scholarly journals Interleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells

1997 ◽  
Vol 185 (3) ◽  
pp. 461-470 ◽  
Author(s):  
Mercedes Rincón ◽  
Juan Anguita ◽  
Tetsuo Nakamura ◽  
Erol Fikrig ◽  
Richard A. Flavell
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antigen Presenting Cells ◽  
Interferon Γ ◽  
T Helper Cell ◽  
Th2 Cells ◽  
T Helper ◽  
Key Factor ◽  
Antigen Presenting ◽  
Potent Factor

Interleukin (IL)-4 is the most potent factor that causes naive CD4+ T cells to differentiate to the T helper cell (Th) 2 phenotype, while IL-12 and interferon γ trigger the differentiation of Th1 cells. However, the source of the initial polarizing IL-4 remains unclear. Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells. These results show that the nature of the cytokine (IL-12 or IL-6), which is produced by antigen-presenting cells in response to a particular pathogen, is a key factor in determining the nature of the immune response.

Chemokines and dendritic cells in inflammatory myopathies: Figure 1

2009 ◽  
Vol 68 (3) ◽  
pp. 300-304 ◽  
Author(s):  
A Tournadre ◽  
P Miossec
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Inflammatory Myopathies ◽  
T Helper ◽  
Adaptive Immune ◽  
Antigen Presenting ◽  
Leucocyte Recruitment

This review focuses on the contribution of the local production of chemokines and cytokines and of dendritic cells (DC) to the pathogenesis of inflammatory myopathies. DC are the most efficient professional antigen-presenting cells (APC), which are critical for the development of innate and adaptive immune responses. Chemokines are important mediators of the immune response as they regulate leucocyte recruitment to tissue and play a key role in inflammatory diseases by acting on T-cell and DC migration. Recent advances indicate that the muscle cell itself could participate in the inflammatory process. Furthermore, the T-helper (Th) type 1 and Th17 proinflammatory cytokines, present in myositis samples, are associated with the migration, differentiation and maturation of inflammatory cells and allow a network of interactions between all the components of the immune response. An understanding of such interactions is essential because it can lead to therapeutic applications.

scholarly journals Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Fan ◽  
Zheng Liu ◽  
He Jin ◽  
Jun Yan ◽  
Hua-ping Liang
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Early Stage ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Immune Disorder ◽  
And Function ◽  
Antigen Presenting

Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies.

Isolation of Human Blood Dendritic Cells Using the CMRF-44 Monoclonal Antibody: Implications for Studies on Antigen-Presenting Cell Function and Immunotherapy

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3708-3716 ◽  
Author(s):  
D.B. Fearnley ◽  
A.D. McLellan ◽  
S.I. Mannering ◽  
B.D. Hock ◽  
D.N.J. Hart
Keyword(s):  
Monoclonal Antibody ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Cell Clone ◽  
Antigen Uptake ◽  
T Cell Clone ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications. Freshly isolated DC or DC precursors may be preferable for studies of antigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The majority of DC circulating in blood do not express any known DC lineage specific markers, but can be identified by CMRF-44 labeling after a brief period of in vitro culture. The sequential acquisition of DC activation antigens allows the identification of two stages of DC maturation/activation. Cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )α, enhance both phases of this process, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype. DC positively selected using CMRF-44 possess potent allostimulatory activity and are efficient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses. CMRF-44+ DC are also more potent than other APC types at restimulation of a chronic myeloid leukemia peptide specific T-cell clone. The use of a purified population of freshly isolated DC may be advantageous in attempts to initiate, maintain, and direct immune responses for immunotherapeutic applications.

scholarly journals TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rikio Yabe ◽  
Soo-Hyun Chung ◽  
Masanori A. Murayama ◽  
Sachiko Kubo ◽  
Kenji Shimizu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Bone Marrow Cells ◽  
Dendritic Cell Maturation ◽  
Mouse Bone Marrow ◽  
Gm Csf ◽  
Good Target ◽  
Antigen Presenting ◽  
Dc Maturation

AbstractTARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. However, the function of this molecule in the regulation of the immune system is unclear. Here, we show that Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in Tarm1–/– mice. T cell priming against type 2 collagen is suppressed in Tarm1–/– mice and antigen-presenting ability of GM-CSF-induced dendritic cells (GM-DCs) from Tarm1–/– mouse bone marrow cells is impaired. We show that type 2 collagen is a functional ligand for TARM1 on GM-DCs and promotes DC maturation. Furthermore, soluble TARM1-Fc and TARM1-Flag inhibit DC maturation and administration of TARM1-Fc blocks the progression of CIA in mice. These results indicate that TARM1 is an important stimulating factor of dendritic cell maturation and could be a good target for the treatment of autoimmune diseases.

scholarly journals Cytotoxic and antigen presenting functions of T helper-1-activated dendritic cells

2012 ◽  
Vol 1 (4) ◽  
pp. 566-568 ◽  
Author(s):  
Nicolas Larmonier ◽  
Bernard Bonnotte ◽  
Emmanuel Katsanis
Keyword(s):  
Dendritic Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Antigen Presenting
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