共查询到20条相似文献,搜索用时 187 毫秒
1.
Yang Li Li-dan Zhao Lu-sha Tong Su-ning Qian Yan Ren Lei Zhang Xin Ding Yang Chen Yan-xia Wang Wen Zhang Xiao-feng Zeng Feng-chun Zhang Fu-lin Tang Xuan Zhang De-nian Ba Wei He Xue-tao Cao Peter E Lipsky 《Arthritis research & therapy》2012,14(3):R123-17
Introduction
CD200 is a type I transmembrane glycoprotein that can regulate the activation threshold of inflammatory immune responses, polarize cytokine production, and maintain immune homeostasis. We therefore evaluated the functional status of CD200/CD200 receptor 1 (CD200R1) interactions in subjects with systemic lupus erythematosus (SLE).Methods
Serum CD200 level was detected by ELISA. The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells (DCs) was examined by flow cytometry, and then compared between SLE patients and healthy controls. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidyl ester and annexin V/propidium iodide for evaluation of the effect of CD200 on cell proliferation and apoptosis. In addition, the effect of CD200 on DC function was determined by transwell migration assay as well as by measurement of binding and phagocytosis of apoptotic cells.Results
In SLE patients, the number of CD200+ cells and the level of soluble CD200 were significantly higher than in healthy controls, whereas the expression of CD200R1 by CD4+ T cells and DCs was decreased. Furthermore, the increased CD200 expression by early apoptotic cells contributed to their diminished binding and phagocytosis by DCs in SLE. Importantly, the engagement of CD200 receptor on CD4+ T cells with CD200-Fc fusion protein in vitro reduced the differentiation of T-helper type 17 cells and reversed the defective induction of CD4+CD25highFoxP3+ T cells by transforming growth factor beta in SLE patients. Conversely, blockade of CD200-CD200R1 interaction with anti-CD200R1 antibody promoted CD4+ T-cell proliferation.Conclusion
CD200 and CD200R1 expression and function are abnormal in SLE and may contribute to the immunologic abnormalities in SLE. 相似文献2.
Rauen T Hedrich CM Juang YT Tenbrock K Tsokos GC 《The Journal of biological chemistry》2011,286(50):43437-43446
3.
Michael Bonelli Lisa G?schl Stephan Blüml Thomas Karonitsch Carl-Walter Steiner Günter Steiner Josef S Smolen Clemens Scheinecker 《Arthritis research & therapy》2014,16(2):R104
Introduction
Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, which can affect different organs. Increased proportions of CD4+CD25-Foxp3+ T cells have been described in SLE patients. The exact role of this cell population in SLE patients still remains unclear. We therefore analyzed this T cell subset in a large cohort of SLE patients with different organ manifestations.Methods
Phenotypic analyses, proportions and absolute cell numbers of CD4+CD25-Foxp3+ T cells were determined by flow cytometry (FACS) in healthy controls (HC) (n = 36) and SLE patients (n = 61) with different organ manifestations. CD4+CD25-Foxp3+ T cells were correlated with clinical data, the immunosuppressive therapy and different disease activity indices. In patients with active glomerulonephritis, CD4+CD25-Foxp3+ T cells were analyzed in urine sediment samples. Time course analyses of CD4+CD25-Foxp3+ T cells were performed in patients with active disease activity before and after treatment with cyclophosphamide and prednisone.Results
CD4+CD25-Foxp3+ T cells were significantly increased in active SLE patients and the majority expressed Helios. Detailed analysis of this patient cohort revealed increased proportions of CD4+CD25-Foxp3+ T cells in SLE patients with renal involvement. CD4+CD25-Foxp3+ T cells were also detected in urine sediment samples of patients with active glomerulonephritis and correlated with the extent of proteinuria.Conclusion
CD4+CD25-Foxp3+ T cells resemble regulatory rather than activated T cells. Comparative analysis of CD4+CD25-Foxp3+ T cells in SLE patients revealed a significant association of this newly described cell population with active nephritis. Therefore CD4+CD25-Foxp3+ T cells might serve as an important tool to recognize and monitor SLE patients with renal involvement. 相似文献4.
Jessica Nadigel David Préfontaine Carolyn J Baglole Fran?ois Maltais Jean Bourbeau David H Eidelman Qutayba Hamid 《Respiratory research》2011,12(1):149
Background
Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways. We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.Methods
Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects. TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood. CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors. PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.Results
No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects. However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells. Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression. CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ. Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.Conclusions
Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD. CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production. These results provide a new perspective on the role of CD8+ T cells in COPD. 相似文献5.
Giuseppe Nocentini Alessia Alunno Maria Grazia Petrillo Onelia Bistoni Elena Bartoloni Sara Caterbi Simona Ronchetti Graziella Migliorati Carlo Riccardi Roberto Gerli 《Arthritis research & therapy》2014,16(5)
Introduction
CD4+CD25low/-GITR+ T lymphocytes expressing forkhead box protein P3 (FoxP3) and showing regulatory activity have been recently described in healthy donors. The objective of the study was to evaluate the proportion of CD4+CD25low/-GITR+ T lymphocytes within CD4+ T cells and compare their phenotypic and functional profile with that of CD4+CD25highGITR− T lymphocytes in systemic lupus erythematosus (SLE) patients.Methods
The percentage of CD4+CD25low/-GITR+ cells circulating in the peripheral blood (PB) of 32 patients with SLE and 25 healthy controls was evaluated with flow cytometry. CD4+CD25low/-GITR+ cells were isolated with magnetic separation, and their phenotype was compared with that of CD4+CD25highGITR− cells. Regulatory activity of both cell subsets was tested in autologous and heterologous co-cultures after purification through a negative sorting strategy.Results
Results indicated that CD4+CD25low/-GITR+ cells are expanded in the PB of 50% of SLE patients. Expansion was observed only in patients with inactive disease. Phenotypic analysis demonstrated that CD4+CD25low/-GITR+ cells display regulatory T-cell (Treg) markers, including FoxP3, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), transforming growth factor-beta (TGF-β), and interleukin (IL)-10. In contrast, CD4+CD25highGITR− cells appear to be activated and express low levels of Treg markers. Functional experiments demonstrated that CD4+CD25low/-GITR+ cells exert a higher inhibitory activity against both autologous and heterologous cells as compared with CD4+CD25highGITR− cells. Suppression is independent of cell contact and is mediated by IL-10 and TGF-β.Conclusions
Phenotypic and functional data demonstrate that in SLE patients, CD4+CD25low/-GITR+ cells are fully active Treg cells, possibly representing peripheral Treg (pTreg) that are expanded in patients with inactive disease. These data may suggest a key role of this T-cell subset in the modulation of the abnormal immune response in SLE. Strategies aimed at expanding this Treg subset for therapeutic purpose deserve to be investigated. 相似文献6.
Xiujuan Zhang Dongrui Zhou Ming Zhao Yongqi Luo Peng Zhang Zuhong Lu Qianjin Lu 《Molecular biotechnology》2010,46(3):243-249
Demethylation of CD11a (ITGAL; GeneID:3683; HGNC: 6148) and CD70 (TNFSF7; GeneID:970; HGNC:11937) regulatory regions in CD4+ T cells contributes to the development of autoreactivity and autoantibody overstimulation in systemic lupus erythematosus
(SLE). In this study, we present a novel approach for measuring the methylation status of CD11a and CD70 promoter sequences.
The procedure combines the standard method of bisulfite conversion of methylated CpG pairs with high-throughput oligonucleotide
microarray-based technology that allows for rapid quantification of deoxycytosine and deoxymethylcytosine content in bisulfite-treated
DNA samples. The microarrays were first used to generate a standard curve from fully methylated and fully unmethylated DNA
samples using a one-dimensional linear regression equation that calculated fluorescence emission as a function of methylation
levels. The methylation status of the CD70 and CD11a promoters in SLE and control CD4+ T cell samples were measured, and the microarray prediction was found to be highly accurate when compared to bisulfite sequencing.
Furthermore, the microarrays were able to detect differences in the methylation status between SLE patient and healthy control
samples. These results indicate that our new microarray-based assay could prove to be a highly reliable, rapid, and cost effective
diagnostic and prognostic test for SLE. 相似文献
7.
Sobel ES Brusko TM Butfiloski EJ Hou W Li S Cuda CM Abid AN Reeves WH Morel L 《Arthritis research & therapy》2011,13(3):R106
Introduction
CD25+ FOXP3+ CD4+ regulatory T cells (Tregs) are induced by transforming growth factor β (TGFβ) and further expanded by retinoic acid (RA). We have previously shown that this process was defective in T cells from lupus-prone mice expressing the novel isoform of the Pbx1 gene, Pbx1-d. This study tested the hypothesis that CD4+ T cells from systemic lupus erythematosus (SLE) patients exhibited similar defects in Treg induction in response to TGFβ and RA, and that PBX1-d expression is associated with this defect. 相似文献8.
Marc Beyer Hongwei Wang Nina Peters Sandra Doths Cordula Koerner-Rettberg Peter JM Openshaw Jürgen Schwarze 《Respiratory research》2005,6(1):70
Background
The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV).Methods
Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c+ CD8+ and CD11c- CD8+ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8+ T cells was assessed by quantitative PCR.Results
Following RSV infection CD11c+ CD8+ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8+ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8+ T cells in the absence of RSV infection, its mRNA was expressed in CD8+ T cells of both naïve and RSV infected mice. CD11c+, but not CD11c-, CD8+ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c+ CD8+ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo.Conclusion
CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo. 相似文献9.
Park MJ Min SY Park KS Cho YG Cho ML Jung YO Park HS Chang SH Cho SG Min JK Park SH Kim HY 《Arthritis research & therapy》2008,10(1):R11-10
Introduction
The present study was devised to understand the role of systemic indoleamine 2,3-dioxygenase (IDO) in the tolerance induction for orally tolerized mice in collagen-induced arthritis (CIA). We examined whether IDO-expressing dendritic cells (DCs) are involved in the generation of CD4+CD25+ regulatory T cells during the induction of oral tolerance in a murine CIA model.Methods
Type II collagen was fed six times to DBA/1 mice beginning 2 weeks before immunization, and the effect on arthritis was assessed. To examine the IDO expression, the DCs of messenger RNA and protein were analyzed by RT-PCR and Flow cytometry. In addition, a proliferative response assay was also carried out to determine the suppressive effects of DCs through IDO. The ability of DCs expressing IDO to induce CD4+CD25+ T regulatory cells was examined.Results
CD11c+ DCs in Peyer's patches from orally tolerized mice expressed a higher level of IDO than DCs from nontolerized CIA mice. IDO-expressing CD11c+ DCs were involved in the suppression of type II collagen-specific T-cell proliferation and in the downregulation of proinflammatory T helper 1 cytokine production. The suppressive effect of IDO-expressing CD11c+ DCs was mediated by Foxp3+CD4+CD25+ regulatory T cells.Conclusion
Our data suggest that tolerogenic CD11c+ DCs are closely linked with the induction of oral tolerance through an IDO-dependent mechanism and that this pathway may provide a new therapeutic modality to treat autoimmune arthritis. 相似文献10.
11.
12.
Zhi-Yong Xiao Shao-Hui Chen Jun-Ping Cheng Wen-Xia Zhou Yong-Xiang Zhang Ri-Fang Yang Liu-Hong Yun 《Arthritis research & therapy》2012,14(6):R235
Introduction
Naturally occurring CD4+CD25+ regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune diseases. We have examined the effects of Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL/lpr autoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27 involves modulation of CD4+CD25+ Treg cells has also been investigated.Methods
Female MRL/lpr mice that spontaneously develop lupus were treated orally by gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of parental female DBA/2 splenic lymphocytes, characterized by immunocomplex-mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD mice for 12 weeks. Nephritic symptoms were monitored and the percentage of CD4+CD25+FoxP3+ Treg peripheral blood leukocyte was detected with mouse regulatory T cell staining kit by flowcytometry. Purified CD4+CD25+ Tregs were assessed for immune suppressive activity using the mixed lymphocyte reaction.Results
The life-span of MRL/lpr mice treated with Y27 for 10 weeks was significantly prolonged, proteinuria and renal lesion severity were ameliorated, and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA antibodies were decreased. Similar results were found in chronic GVHD mice. Administration of Y27 had little impact on percentage of the peripheral blood lymphocyte CD4+CD25+Foxp3+ Treg cells in both groups of mice. In contrast, the suppressive capacity of CD4+CD25+ Treg cells in splenocytes was markedly augmented in Y27-treated mice ex vivo.Conclusions
Experimental evidence of the protect effects of Y27 against autoimmune nephritis has been shown. The mechanism may involve enhancement of the suppressive capacity of CD4+CD25+ Treg cells. 相似文献13.
Xuebing Feng Dandan Wang Jingjing Chen Lin Lu Bingzhu Hua Xia Li Betty P. Tsao Lingyun Sun 《PloS one》2012,7(12)
Objective
To observe the proportion of peripheral T follicular helper (Tfh) cells in patients with systemic lupus erythematosus (SLE) and to assess the role of steroids on Tfh cells from SLE patients.Methods
Peripheral blood mononuclear cells (PBMCs) from 42 SLE patients and 22 matched healthy subjects were collected to assess proportions of circulating CXCR5+PD1+/CD4+ T cells (Tfh), CD4+CCR6+ T cells (Th17-like) and CD19+CD138+ plasma cells by flow cytometry. 8 of the patients had their blood redrawn within one week after receiving methylprednisolone pulse treatment. Disease activity was evaluated by SLE disease activity index. To test the effect of IL-21 and corticosteroids on Tfh cells in vitro, PBMCs harvested from another 15 SLE patients were cultured with medium, IL-21, or IL-21+ dexamethasone for 24 hours and 72 hours. PBMCs from an independent 23 SLE patients were cultured with different concentrations of dexamethasone for 24 hours.Results
Compared to normal controls, percentages of circulating Tfh cells, but not Th17 cells, were elevated in SLE patients and correlated with disease activity. Proportions of Tfh cells in SLE patients were positively correlated with those of plasma cells and serum levels of antinuclear antibodies. After methylprednisolone pulse treatment, both percentages and absolute numbers of circulating Tfh cells were significantly decreased. In vitro cultures showed an increase of Tfh cell proportion after IL-21 stimulation that was totally abolished by the addition of dexamethasone. Both 0.5 and 1 µM dexamethasone decreased Tfh cells dose dependently (overall p = 0.013).Conclusions
We demonstrated that elevated circulating Tfh cell proportions in SLE patients correlated with their disease activities, and circulating levels of plasma cells and ANA. Corticosteroids treatment down-regulated aberrant circulating Tfh cell proportions both in vivo and in vitro, making Tfh cells a new treatment target for SLE patients. 相似文献14.
Yumi Park Jinsook Lim Seon Young Kim Gye Cheol Kwon Sun Hoe Koo Jimyung Kim 《Microbiology and immunology》2020,64(7):532-539
Immunologic abnormalities of natural killer (NK) cells and T cells play a role in the pathogenesis of systemic lupus erythematosus (SLE). CD161 is expressed on most of the NK cells and on some T cells. The quantities of CD161-expressing cells and expression levels of CD161 were analyzed in T cells and NK cells from patients with SLE compared with normal controls. The expression of CD161 on NK cells, NKT cells, CD4+ T cells, and CD8+ T cells in peripheral blood from patients with inactive SLE and active SLE, and from the normal controls group were determined using flow cytometry. The frequency and expression level of CD161 in the lymphocyte subsets and its relationship with the quantity of regulatory T cells, anti-double stranded DNA antibody, and the titer of antinuclear antibody were evaluated. Both the percentages of the CD161+ subpopulation and the mean fluorescence intensities (MFIs) of CD161 in CD8+ T cells and NKT cells decreased significantly in SLE patients compared with normal controls (P < .001). The CD161 expression in CD8+ T cells and NKT cells also decreased in the anti-dsDNA (+) group (P < .05). The counts of Treg cells were lower in SLE patients and were weakly correlated with the percentage of the CD161 subpopulation (r = 0.229, P = .016) and the MFIs of CD161 expression in CD8+ T cells (r = .232, P = .014). The frequencies and levels of CD161 expression on CD8+ T cells and NKT cells were reduced in SLE patients, suggesting that an abnormality of these cells was related to the pathogenesis of SLE. 相似文献
15.
A Matsui H Yokoo Y Negishi Y Endo-Takahashi NA Chun I Kadouchi R Suzuki K Maruyama Y Aramaki K Semba E Kobayashi M Takahashi T Murakami 《PloS one》2012,7(8):e44080
Background
Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1), recruits immature myeloid-derived cells and enhances early tumor progression.Methodology/Principal Findings
CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b+Gr1+ myeloid-derived cells at tumor sites in mice and promoted CD31+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b+Gr1highF4/80− cells (∼90%) with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b+Gr1+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation.Conclusions/Significance
These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis. 相似文献16.
Mariel Garcia-Chagollan Luis F Jave-Suarez Jesse Haramati Pedro E Sanchez-Hernandez Adriana Aguilar-Lemarroy Miriam R Bueno-Topete Ana L Pereira-Suarez Mary Fafutis-Morris Angel Cid-Arregui Susana del Toro-Arreola 《Journal of biomedical science》2013,20(1):60
Background
The NKG2D receptor confers important activating signals to NK cells via ligands expressed during cellular stress and viral infection. This receptor has generated great interest because not only is it expressed on NK cells, but it is also seen in virtually all CD8+ cytotoxic T cells and is classically considered absent in CD4+ T cells. However, recent studies have identified a distinctive population of CD4+ T cells that do express NKG2D, which could represent a particular cytotoxic effector population involved in viral infections and chronic diseases. On the other hand, increased incidence of human papillomavirus-associated lesions in CD4+ T cell-immunocompromised individuals suggests that CD4+ T cells play a key role in controlling the viral infection. Therefore, this study was focused on identifying the frequency of NKG2D-expressing CD4+ T cells in patients with cervical intraepithelial neoplasia (CIN) 1. Additionally, factors influencing CD4+NKG2D+ T cell expansion were also measured.Results
Close to 50% of patients with CIN 1 contained at least one of the 37 HPV types detected by our genotyping system. A tendency for increased CD4+ T cells and CD8+ T cells and decreased NK cells was found in CIN 1 patients. The percentage of circulating CD4+ T cells co-expressing the NKG2D receptor significantly increased in women with CIN 1 versus control group. Interestingly, the increase of CD4+NKG2D+ T cells was seen in patients with CIN 1, despite the overall levels of CD4+ T cells did not significantly increase. We also found a significant increase of soluble MICB in CIN 1 patients; however, no correlation with the presence of CD4+NKG2D+ T cells was seen. While TGF-beta was significantly decreased in the group of CIN 1 patients, both TNF-alpha and IL-15 showed a tendency to increase in this group.Conclusions
Taken together, our results suggest that the significant increase within the CD4+NKG2D+ T cell population in CIN 1 patients might be the result of a chronic exposure to viral and/or pro-inflammatory factors, and concomitantly might also influence the clearance of CIN 1-type lesion. 相似文献17.
Guoping Shi Dan Li Xiaojing Li Jing Ren Jingjing Xu Liang Ding Huan Dou Yayi Hou 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):1-13
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by systemic chronic inflammation that can affect multiple major organ systems. Although the etiology of SLE is known to involve a variety of factors such as the environment, random factors and genetic susceptibility, the exact role of CD11b+Gr1+ myeloid cells in lupus progression is not fully understood. Myeloid-derived CD11b+Gr1+ cells are thought to be a heterogeneous group of immature myeloid cells with immune function. Some studies have reported that CD11b+Gr1+ cells and the activation of mTOR pathway are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, it is still not clarified about the mechanism of influence of lupus microenvironment and mTOR signaling on CD11b+Gr1+ cells. In the present study, we found that the percentage of CD11b+Gr1+ cells increased prior to the abnormal changes of Th17, Treg, T and B cells during lupus development. TLR7 and IFN-α signaling synergized to promote CD11b+Gr1+ cell accumulation in an mTOR-dependent manner. Moreover, compared to a traditional mTOR inhibitor, INK128 inhibited more effectively the disease activity via regulating CD11b+Gr1+ cell expansion and functions. Furthermore, TLR7/IFN-α-modified CD11b+Gr1+ cells promoted unbalance of Th17/Tregs and were inclined to differentiate into macrophages via the mTOR pathway. In conclusion, CD11b+Gr1+ cells increased in the early stages of the lupus progression and mTOR pathway was critical for CD11b+Gr1+ cells in lupus development, suggesting the changes of inflammation-induced CD11b+Gr1+ cells initate lupus development. We also provide evidence for the first time that INK128, a second generation mTOR inhibitor, has a good therapeutic action on lupus development by regulating CD11b+Gr1+ cells. 相似文献
18.
19.
《Cryobiology》2016,72(3):507-510
Several studies report on lymphocyte phenotypic and functional abnormalities in Systemic Lupus Erythematosus (SLE). Freezing and thawing may alter functional and phenotypic properties of cells. We assessed the effect of the freezing/thawing process (F/T) on Th1 (CD3+CD4+CCR4−CXCR3+CCR5+), Th2 (CD3+CD4+CCR5−CXCR3−CCR4+), Th17 (CD3+CD4+CCR6+CD161+), and Treg (CD3+CD4+CD25highCD127-) cell cultures in healthy controls and SLE patients. F/T was associated with decreased frequency of Th2 and Th17 cells in cultures from SLE patients but not from controls. F/T was also associated with increased frequency of apoptotic cells, as measured by annexin V labeling, in all T cell subtypes analyzed, as well as increased cell proliferation, as measured by Ki-67 labeling, in all cells except Th1 from SLE patients. Thus, F/T can have differentiated effects on T lymphocyte subtypes from SLE patients and controls, and can have significant effects on cell death and proliferation. These findings should be carefully considered when designing and interpreting studies on functional and phenotypic aspects of T lymphocytes in SLE. 相似文献
20.
Jianchang Zhou Paul C. Dimayuga Xiaoning Zhao Juliana YanoWai Man Lio Portia TrinidadTomoyuki Honjo Bojan CercekPrediman K. Shah Kuang-Yuh Chyu 《Biochemical and biophysical research communications》2014