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Th17 Treg leukemia

Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
Mingli Xiang, Li Guo, Yan Ma, Yi Li
To discuss the expression of T helper cell 17 (Th17) cells and CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in peripheral blood (PB) of patients with acute leukemia (AL), and to explore the relationship between them and disease prognosis. 40 patients diagnosed with acute leukemia in The First Affiliated Hospital of Zhengzhou University from July 2012 to August 2014 were selected as the observation group. Meanwhile, 40 healthy people were taken as the control group. Flow Cytometry Method (FCM) was used to detect the level of Th17 cells and CD4(+) CD25(+) Foxp3(+) cells in peripheral blood of the two groups, and enzyme-linked immuno sorbent assay (ELISA) method was used to test the level of IL17 and TGF-β in peripheral blood of two groups; reverse transcription-polymerase chain reaction (RT-PCR) was adopted to analyze the mRNA levels of RORγT and Foxp3 in peripheral blood...
November 2016: Pakistan Journal of Pharmaceutical Sciences
Nannan Pang, Rui Zhang, Jinhua Li, Zhenghao Zhang, Hailong Yuan, Gang Chen, Fang Zhao, Lei Wang, Haizhou Cao, Jianhua Qu, Jianbing Ding
OBJECTIVE: This study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL). METHODS: Totally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR...
November 2016: International Immunopharmacology
Astrid Olsnes Kittang, Shahram Kordasti, Kristoffer Evebø Sand, Benedetta Costantini, Anne Marijn Kramer, Pilar Perezabellan, Thomas Seidl, Kristin Paulsen Rye, Karen Marie Hagen, Austin Kulasekararaj, Øystein Bruserud, Ghulam J Mufti
Although the role of CD4(+) T cells and in particular Tregs and Th17 cells is established in myelodysplastic syndrome(MDS), the contribution of other components of immune system is yet to be elucidated fully. In this study we investigated the number and function of myeloid derived suppressor cells (MDSCs) in fresh peripheral blood and matched bone marrow samples from 42 MDS patients and the potential correlation with risk of disease progression to acute myeloid leukemia (AML). In peripheral blood, very low-/low risk patients had significantly lower median MDSC number (0...
February 2016: Oncoimmunology
Tian Tian, Shuang Yu, Lu Liu, Fuzhong Xue, Cunzhong Yuan, Min Wang, Chunyan Ji, Daoxin Ma
BACKGROUND: T helper (Th) cells immune regulation is important for the pathogenesis of acute myeloid leukemia (AML). Recurrent Th abnormalities in AML peripheral blood were reported, while the comprehensive status of various Th subsets is rarely investigated in bone marrow (BM) microenvironment which is the origin of AML leukemic blast cells. METHODS: BM was extracted from 48 newly-diagnosed (ND), 34 complete-remission (CR), 19 relapsed-refractory AML patients and 15 controls...
2015: PloS One
Mehdi Yousefi, Ali Akbar Movassaghpour, Karim Shamsasenjan, Ghasem Ghalamfarsa, Sanam Sadreddini, Farhad Jadidi-Niaragh, Mohammad Hojjat-Farsangi
While Tregs maintain self-tolerance and inhibit antitumor responses, T helper (Th)17 cells may enhance inflammatory and antitumor responses. The balance between these two important T-cell subsets has been skewed in many immunopathologic conditions such as autoimmune and cancer diseases. B-cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western world and is characterized with monoclonal expansion of B lymphocytes. There is evidence which implies that the progression of CLL is associated with expansion of Treg and downregulation of Th17 cells...
2015: Future Oncology
M Levite
Dopamine, a principal neurotransmitter, deserves upgrading to 'NeuroImmunotransmitter' thanks to its multiple, direct and powerful effects on most/all immune cells. Dopamine by itself is a potent activator of resting effector T cells (Teffs), via two independent ways: direct Teffs activation, and indirect Teffs activation by suppression of regulatory T cells (Tregs). The review covers the following findings: (i) T cells express functional dopamine receptors (DRs) D1R-D5R, but their level and function are dynamic and context-sensitive, (ii) DR membranal protein levels do not necessarily correlate with DR mRNA levels, (iii) different T cell types/subtypes have different DR levels and composition and different responses to dopamine, (iv) autoimmune and pro-inflammatory T cells and T cell leukaemia/lymphoma also express functional DRs, (v) dopamine (~10(-8) M) activates resting/naive Teffs (CD8(+) >CD4(+) ), (vi) dopamine affects Th1/Th2/Th17 differentiation, (vii) dopamine inhibits already activated Teffs (i...
January 2016: Acta Physiologica
Jing-Jing Yu, Gang Chen, Nan-Nan Pang, Xin-Hong Guo, Lei Wang, Fang Zhao, Ming-Fang Tan, Jian-Hua Qu
OBJECTIVE: This study was to investigate the mRNA expression of T-bet, GATA-3, ROR γt and Foxp3 mRNA in peripheral blood of patients with chronic lymphocytic leukemia (CLL) in different stages and explore their potential role in the pathogenesis and clinical diagnosis. METHODS: A total of 46 newly diagnosed and untreated patients with CLL was chosen as patient group, including 16 patients in the stage of Binet A, 15 in the stage of Binet B, and 15 in the stage of Binet C; 20 healthy persons were selected as controls...
February 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
Deepesh P Lad, Subhash Varma, Neelam Varma, Man Updesh Singh Sachdeva, Parveen Bose, Pankaj Malhotra
The reasons for progression and autoimmune cytopenias (AIC) in chronic lymphocytic leukemia (CLL) are not entirely clear, with previous studies suggesting a role for regulatory T-cells (Treg). In this study we prospectively studied Treg (CD3+CD4+CD25highCD127low), interleukin-10 (IL-10) producing Treg and T-helper 17 (Th17) (CD3+CD4+IL-17+) cells in 40 treatment-naive patients with CLL. The percentage of Th17 and not Treg cells was significantly higher in the AIC cohort than in those without AIC (p<0.0001)...
2015: Leukemia & Lymphoma
C Deligne, A Metidji, W-H Fridman, J-L Teillaud
The long-lasting clinical response by lymphoma patients to anti-CD20 therapy has been attributed to the induction of an anti-tumor adaptive immunity. We previously demonstrated that a CD4-dependent mechanism is responsible for the long-term protection of CD20(+) tumor-bearing mice by anti-CD20 treatment. Here, we compare tumor immunity in tumor-bearing animals that did or did not receive anti-CD20 treatment. Splenic CD4(+)FoxP3(+) regulatory T cells (Tregs) expanded substantially in untreated mice that exhibited then a reduced survival, whereas Tregs depletion led to long-term survival of the animals, suggesting the establishment of a Treg-dependent immunosuppressive environment after tumor injection...
April 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Dijiao Tang, Qian Niu, Nenggang Jiang, Jingjing Li, Qin Zheng, Yongqian Jia
UNLABELLED: Objective : In this study, we aimed to investigate changes of peripheral Th17 and Treg cells frequencies in the newly-diagnosed Chronic Lymphocytic Leukemia (CLL) patients for 12 months. Methods : In this research, 50 CLL patients were enrolled. Circulating Th1, Th17 cells and CD4+CD25+Foxp3+Treg cells were analyzed by flow cytometry. Plasma levels of related cytokines were detected by enzyme-linked immuno sorbent assay (ELISA). The study was carried out from January 2012 to October 2013 at Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P...
September 2014: Pakistan Journal of Medical Sciences Quarterly
Thorsten Braun, Pierre Fenaux
Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD...
December 2013: Best Practice & Research. Clinical Haematology
Yuan-xin Sun, Hai-li Kong, Chuan-fang Liu, Shuang Yu, Tian Tian, Dao-xin Ma, Chun-yan Ji
BACKGROUND: Immunological disorder has shown to be related to the pathogenesis of acute myeloid leukemia (AML). The microenvironment of AML is immunosuppressive, favoring the survival of malignant hematopoietic cells. However, the systematic research on AML abnormal immune microenvironment, especially the T helper (Th) cells imbalance, remains unsettled. DESIGN AND METHODS: The levels of cytokines in bone marrow plasma including Th1-associated cytokine (IFN-γ), Th2-associated cytokine (IL-4), Th17-associated cytokines (IL-17, IL-6, TGF-β, and IL-21), regulatory T cell (Treg)-associated cytokines (IL-35 and IL-10) and Th22-associated cytokine (IL-22) were examined by enzyme-linked immunosorbent assay (ELISA) in AML patients and controls...
February 2014: Human Immunology
Iwona Hus, Agnieszka Bojarska-Junak, Sylwia Chocholska, Waldemar Tomczak, Justyna Woś, Anna Dmoszyńska, Jacek Roliński
Th17 cells, a recently discovered subset of T helper cells that secrete IL-17A, can affect the inflammation process autoimmune and cancer diseases development. The purpose of this study was to evaluate the role of Th17 cells and IL17A in biology of CLL. The study group included 294 untreated CLL patients in different clinical stages. Here, we show that higher Th17 and IL-17A values were associated with less advanced clinical stage of CLL. Th17 cells' percentages in PB were lower in patients who died due to CLL during follow-up due to CLL (as compared to surviving patients) and in patients responding to first-line therapy with fludarabine-based regimens (as compared to non-responders)...
2013: PloS One
Xuehai Wang, Martin Marcinkiewicz, Yaned Gatain, Maxime Bouchard, Jianning Mao, Michel Tremblay, Noriko Uetani, Silva Hanissian, Shijie Qi, Jiangping Wu, Hongyu Luo
Myeloid leukemia factor 1-interacting protein (MLF1-IP) has been found to exert functions in mitosis, although studies have been conducted only in cell lines up to now. To understand its roles during ontogeny and immunity, we analyzed its mRNA expression pattern by in situ hybridization and generated MLF1-IP gene knockout (KO) mice. MLF1-IP was expressed at elevated levels in most rudimentary tissues during the mid-gestation stage, between embryonic day 9.5 (e9.5) and e15.5. It declined afterwards in these tissues, but was very high in the testes and ovaries in adulthood...
2013: PloS One
Yu Yu, Dapeng Wang, Kane Kaosaard, Chen Liu, Jianing Fu, Kelley Haarberg, Claudio Anasetti, Amer A Beg, Xue-Zhong Yu
Transcription factors of the Rel/NF-κB family are known to play different roles in immunity and inflammation, although the putative role of c-Rel in transplant tolerance and graft-versus-host disease (GVHD) remains elusive. We report here that T cells deficient for c-Rel have a dramatically reduced ability to cause acute GVHD after allogeneic bone marrow transplantation using major and minor histocompatibility mismatched murine models. In the study to understand the underlying mechanisms, we found that c-Rel(-/-) T cells had a reduced ability to expand in lymphoid organs and to infiltrate in GVHD target organs in allogeneic recipients...
September 2013: European Journal of Immunology
Di-Jiao Tang, Qian Niu, Ting-Ting Zeng, Neng-Gang Jiang, Yong-Mei Jin, Bin Ding, Qin Zheng, Qing Shi, Jiao Chen, Jiang Yu, Jun Su, Yong-Qian Jia
This study was purposed to investigate the ratio of Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood of patients with chronic lymphocytic leukemia (CLL) and to explore their roles in the pathogenesis and clinical diagnosis. Based on the number of peripheral lymphocytes and treatment condition, the CLL patients were divided into 2 groups: untreated group (n = 30) and remission group (n = 15), the healthy control group (n = 20) was set up as well. The frequencies of Th17 and Treg cells of all cases were detected by flow cytometry (FCM)...
April 2013: Zhongguo Shi Yan Xue Ye Xue za Zhi
M Couturier, B Lamarthée, J Arbez, J-C Renauld, C Bossard, F Malard, F Bonnefoy, M Mohty, S Perruche, P Tiberghien, P Saas, B Gaugler
Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation (allo-HCT), limiting the success of this therapy. Many proinflammatory cytokines secreted following the conditioning regimen have been linked to aGVHD initiation. Interleukin-22 (IL-22) is a cytokine related to IL-10 for its structure and is secreted by T helper type 17 (TH17) cells and innate immune cells. Given the paradoxical role of IL-22 in inflammation with both protective or proinflammatory functions, we investigated whether IL-22 could have a role in aGVHD pathophysiology in a mouse allo-HCT model...
July 2013: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Farhad Jadidi-Niaragh, Ghasem Ghalamfarsa, Ali Memarian, Hossein Asgarian-Omran, Seyed Mohsen Razavi, Abdolfattah Sarrafnejad, Fazel Shokri
Little is known about the immunobiology of interleukin-17 (IL-17)-producing T cells and regulatory T cells (Treg) in chronic lymphocytic leukemia (CLL). In this study, the frequencies of Th17, Tc17, and CD39(+) Treg cells were enumerated in peripheral T cells isolated from 40 CLL patients and 15 normal subjects by flow cytometry. Our results showed a lower frequency of Th17 and Tc17 cells in progressive (0.99 ± 0.12 % of total CD3(+)CD4(+) cells; 0.44 ± 0.09 % of total CD8(+) cells) compared to indolent patients (1...
April 2013: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Su M Metcalfe, Tarek M Fahmy
Nanotechnology permits the design of therapeutic devices with defined structure and molecular composition. Modular designs employing surface-bound ligands provide specific homing devices for loaded cargo, and biocompatible and biodegradable constructs provide surrogate temporary microenvironments. We first present a case for developing 'smart' modular constructs as immunogenic vaccines to prime immune memory against specific pathogens where current vaccines fail. Second, we argue that nanotherapeutic intervention can harness pivotal molecular pathways recently discovered to regulate lineage development between pathogenic TH17 cells associated with autoimmune disease, versus tolerogenic regulatory T cells (Treg)...
February 2012: Trends in Molecular Medicine
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