15 results on '"Ludvig Linton"'
Search Results
2. Supplemental figure S1-S7 from Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness
- Author
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Ola Winqvist, Amir Sherif, Per Marits, Max Winerdal, Markus Johansson, Benny Holmström, Johan Hansson, Farhood Alamdari, Janos Vasko, Robert Rosenblatt, Emma A. Bergman, Ludvig Linton, Ali A. Zirakzadeh, Ciputra A. Hartana, David Krantz, and Malin E. Winerdal
- Abstract
Supplemental figure 1 illustrates gating strategy appliead to FACS data. Supplemental figure 2 shows gene expression correlation to Treg frequency overlaid on KEGG bladder cancer pathway. Supplemental figure 3 shows expression of functional Treg markers in FOXP3+ and FOXP3- cells from PBMCs and TILs. Supplemental figure 4 compares the phenotype of TIL Tregs from MIBC and non-MIBC tumors. Supplemental figure 5 illustrates post-sort purity sorted populations. Supplemental figure 6 illustrates the correlation of Treg frequency at tumor sublocations to tumor stage and survival. Supplemental figure 7 shows expression level of different MMPs in UBC tumor tissue.
- Published
- 2023
3. Data from Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness
- Author
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Ola Winqvist, Amir Sherif, Per Marits, Max Winerdal, Markus Johansson, Benny Holmström, Johan Hansson, Farhood Alamdari, Janos Vasko, Robert Rosenblatt, Emma A. Bergman, Ludvig Linton, Ali A. Zirakzadeh, Ciputra A. Hartana, David Krantz, and Malin E. Winerdal
- Abstract
Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This discrepancy has partly been attributed to the shear misidentification of Tregs, but also to the inflammatory profile of the tumor. Our aim was to determine whether tumor-infiltrating Forkhead box P3+ (FOXP3+) cells confer a stable Treg phenotype and to investigate putative beneficial Treg functions, focusing on tumor-promoting inflammatory pathways in UBC. Patients (n = 52) with suspected UBC were prospectively included. We show, by using a broad range of analytical approaches, that tumor-infiltrating CD4+FOXP3+ T cells in UBC phenotypically, functionally, and epigenetically represent a true Treg population. At the invasive front of UBC tumors, we found an inverse relationship between Treg frequency and expression of matrix metalloproteinase 2 (MMP2), a key proinvasive factor induced by tumor-promoting inflammation. Correspondingly, a significant, dose-dependent Treg-mediated downregulation of MMP2 protein and mRNA expression was observed in both macrophages and UBC cells. Also, we found that Treg frequency specifically at the invasive front positively correlated with survival. Thus, we identify Treg-mediated suppression of MMP2 in the tumor microenvironment as a mechanism explaining the paradoxical positive prognostic impact of tumor-infiltrating Tregs in UBC. Cancer Immunol Res; 6(5); 528–38. ©2018 AACR.
- Published
- 2023
4. Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- Author
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Karin Palmqvist, Emma Ahlén Bergman, Benny Holmström, Ola Winqvist, Ciputra Adijaya Hartana, Johan Hansson, Malin E. Winerdal, Farhood Alamdari, Louise K. Sjöholm, Firas Aljabery, David E. Krantz, Ylva Huge, Amir Sherif, Per Marits, Katrine Riklund, Christian Lundgren, Ludvig Linton, A. Ali Zirakzadeh, Martin Hyllienmark, Markus Johansson, and Sofia Berglund
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,medicine.medical_treatment ,lcsh:Medicine ,DNA methylation ,CD4-positive T lymphocytes ,Urinary bladder neoplasms ,Epigenesis, Genetic ,0302 clinical medicine ,Urologi och njurmedicin ,Genetics (clinical) ,Cells, Cultured ,Aged, 80 and over ,Interleukin-13 ,Interleukin-17 ,FOXP3 ,Cell Differentiation ,Forkhead Transcription Factors ,Middle Aged ,Prognosis ,Neoadjuvant Therapy ,medicine.anatomical_structure ,Treatment Outcome ,CpG site ,030220 oncology & carcinogenesis ,Female ,Lymph ,lcsh:QH426-470 ,T cell ,Malignancy ,Cystectomy ,03 medical and health sciences ,Interferon-gamma ,Immune system ,Drug Therapy ,Genetics ,medicine ,Urology and Nephrology ,Humans ,Cell Lineage ,Molecular Biology ,Aged ,Neoplasm Staging ,business.industry ,Research ,Kirurgi ,lcsh:R ,Sequence Analysis, DNA ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,Cancer research ,CpG Islands ,Surgery ,business ,Developmental Biology - Abstract
Background: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4(+) T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-gamma, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4(+ )T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy. Results: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4(+ )lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4(+) lymphocytes in lymph nodes and blood (lymph nodes vs rumour-infiltrating lymphocytes: IFNG -4229 bp p amp;lt; 0.0001, IL13 -11 bp p amp;lt; 0.05, IL17A -122 bp p amp;lt; 0.01 and FOXP3 -77 bp pamp;gt; 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4(+ )T cells for all four investigated loci, most prominently in IFNG p amp;lt; 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4(+) T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3. Conclusion: Increased lineage commitment in CD4(+) T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4(+) T cell lineages as a useful readout for clinical staging. Funding Agencies|Swedish Cancer foundation; Wallenberg foundation; Swedish Medical Research Council; Regionala forskningsradet i Uppsala-Orebroregionen (RFR in Uppsala-Orebro); Swedish Research Council; Cancer Research Foundation in Norrland, Umea, Sweden; Stiftelsen Emil Anderssons fond for medicinsk forskning, Sundsvall, Sweden
- Published
- 2018
5. Chemokine receptor expression on monocytes from healthy individuals
- Author
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Ludvig Linton, Ola Winqvist, Hans Glise, Martina Jones Kostalla, Katarina Glise Sandblad, and Petra Jones
- Subjects
Adult ,Male ,Receptors, CXCR ,CCR2 ,Immunology ,C-C chemokine receptor type 6 ,Biology ,Flow Cytometry ,Healthy Volunteers ,Monocytes ,Receptors, CCR ,CXCL2 ,Chemokine receptor ,Humans ,Immunology and Allergy ,CXCL10 ,Female ,Receptors, Chemokine ,CCL13 ,CC chemokine receptors ,CCL21 - Abstract
Chronic immune mediated inflammation is characterized by continuous chemokine mediated recruitment and activation of pro-inflammatory cells, monocytes in particular. We believe that an evaluation of the recruitment profile of monocytes during healthy condition is essential for the understanding of cellular response in disease. For this, we have established normal reference values and 95% confidence intervals for receptor expression of 20 chemokine receptors on monocyte subsets; classical (CD14+ CD16−), non-classical (CD14+ CD16+) and HLA-DRhi monocytes from 20 healthy controls using flow cytometry. We demonstrate significant differences in the chemokine receptor expression profiles and high correlation between fraction of cells and level of expression. This is the first global approach to provide a platform for comparable evaluation of cell recruitment during normal and under inflammatory conditions. This will be useful when exploring chemokine–chemokine receptor interactions, inhibition of chemokine signaling and selective removal of migrating cells, which are new treatment strategies in immune mediated diseases.
- Published
- 2015
6. Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness
- Author
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Farhood Alamdari, Ludvig Linton, Emma Ahlén Bergman, Max Winerdal, Johan Hansson, Ola Winqvist, Markus Johansson, David E. Krantz, Janos Vasko, Robert Rosenblatt, Ali Zirakzadeh, Ciputra Adijaya Hartana, Benny Holmström, Malin E. Winerdal, Amir Sherif, and Per Marits
- Subjects
0301 basic medicine ,Male ,Cancer Research ,MMP2 ,Immunology ,Down-Regulation ,chemical and pharmacologic phenomena ,T-Lymphocytes, Regulatory ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Downregulation and upregulation ,law ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Cells, Cultured ,Aged ,Muscle Neoplasms ,Urinary Bladder Cancer ,business.industry ,Case-control study ,Cancer ,Middle Aged ,medicine.disease ,030104 developmental biology ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cancer research ,Carcinoma, Squamous Cell ,Suppressor ,Matrix Metalloproteinase 2 ,Female ,business - Abstract
Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This discrepancy has partly been attributed to the shear misidentification of Tregs, but also to the inflammatory profile of the tumor. Our aim was to determine whether tumor-infiltrating Forkhead box P3+ (FOXP3+) cells confer a stable Treg phenotype and to investigate putative beneficial Treg functions, focusing on tumor-promoting inflammatory pathways in UBC. Patients (n = 52) with suspected UBC were prospectively included. We show, by using a broad range of analytical approaches, that tumor-infiltrating CD4+FOXP3+ T cells in UBC phenotypically, functionally, and epigenetically represent a true Treg population. At the invasive front of UBC tumors, we found an inverse relationship between Treg frequency and expression of matrix metalloproteinase 2 (MMP2), a key proinvasive factor induced by tumor-promoting inflammation. Correspondingly, a significant, dose-dependent Treg-mediated downregulation of MMP2 protein and mRNA expression was observed in both macrophages and UBC cells. Also, we found that Treg frequency specifically at the invasive front positively correlated with survival. Thus, we identify Treg-mediated suppression of MMP2 in the tumor microenvironment as a mechanism explaining the paradoxical positive prognostic impact of tumor-infiltrating Tregs in UBC. Cancer Immunol Res; 6(5); 528–38. ©2018 AACR.
- Published
- 2017
7. Peripheral and Site-Specific CD4+CD28nullT Cells from Rheumatoid Arthritis Patients Show Distinct Characteristics
- Author
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Mary Rieck, Vivianne Malmström, S. Johansson, Ludvig Linton, Omri Snir, Ola Winqvist, R. van Vollenhoven, Jane H. Buckner, and Jennifer Pieper
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Adolescent ,T cell ,Immunology ,chemical and pharmacologic phenomena ,Article ,CCL5 ,Arthritis, Rheumatoid ,Interferon-gamma ,03 medical and health sciences ,Interleukin 21 ,0302 clinical medicine ,CD28 Antigens ,medicine ,Humans ,Cytotoxic T cell ,Aged ,030304 developmental biology ,Interleukin 3 ,Aged, 80 and over ,0303 health sciences ,CD40 ,biology ,hemic and immune systems ,General Medicine ,DNA Methylation ,Middle Aged ,Natural killer T cell ,Molecular biology ,medicine.anatomical_structure ,biology.protein ,Interleukin 12 ,Cytokines ,Female ,Receptors, Chemokine ,030215 immunology - Abstract
Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population.
- Published
- 2014
8. Naïve T cells correlate with mucosal healing in patients with inflammatory bowel disease
- Author
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Per Karlén, Hans Glise, Michael Eberhardson, Mats Karlsson, Ola Winqvist, Maria Lampinen, Ragnar Befrits, Izabella Janczewska, Marie Carlson, and Ludvig Linton
- Subjects
Adult ,Antigens, Differentiation, T-Lymphocyte ,Male ,medicine.medical_specialty ,Lymphocyte Activation ,Severity of Illness Index ,Inflammatory bowel disease ,Gastroenterology ,Flow cytometry ,Immune system ,Crohn Disease ,Antigen ,Intestinal mucosa ,Antigens, CD ,Cell Movement ,Internal medicine ,medicine ,Humans ,Lectins, C-Type ,Intestinal Mucosa ,L-Selectin ,Colitis ,Wound Healing ,medicine.diagnostic_test ,business.industry ,T-Lymphocytes, Helper-Inducer ,Flow Cytometry ,medicine.disease ,Phenotype ,Ulcerative colitis ,Immunology ,Leukocyte Common Antigens ,Colitis, Ulcerative ,Female ,business - Abstract
In previous studies, adaptive immune responses involving T-helper cells have been shown to play an important role in inflammatory bowel diseases (IBDs).The aim of this study was to investigate any correlation between the degree of mucosal inflammation and the phenotype of gut-infiltrating T-helper cells. Biopsies from intestinal mucosa were obtained and intestinal T cells were analyzed with regard to activity and maturation markers. Patients with active colitis (39 with Crohn's disease and 47 with ulcerative colitis) were included and treated with corticosteroids, biologicals or leukocytapheresis. Flow cytometry was used to analyze activation marker expression on gut-infiltrating T-helper cells.Mucosal healing was reflected by almost 100% increase of CD62L expression in mucosal T cells in patients in remission compared to those with active inflammation (p0.01). The frequency of mucosal-naïve CD4(+)CD45RA(+) T cells was reduced by 50% in mucosa displaying remission (5.3% compared to 12% of the total amount and CD4(+) T cells, p0.001). Surprisingly, the proportion of early activated T-helper cells (CD4(+)CD69(+)) did not differ between mucosa in remission and non-remission (43% and 42%, respectively). Moreover, no change in memory T-helper cells (CD4(+)CD45RO(+)) was observed (64% compared to 66%). The findings were independent of diagnosis (Crohn's disease or ulcerative colitis) or mode of treatment.This study suggests that a reduced recruitment of naïve T-helper cells and increased frequency of T-helper cells with lymph node homing marker expression reflect mucosal healing in IBD. Surprisingly, the degree of activation of mucosal T-helper cells did not correlate with disease remission.
- Published
- 2013
9. Profiling of CD4(+) T Cells with Epigenetic Immune Lineage Analysis
- Author
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Emma Ahlén Bergman, Fredrik Piehl, Vivianne Malmström, Ola Winqvist, Ludvig Linton, Michael Eberhardson, Per Marits, and Peter Janson
- Subjects
CD4-Positive T-Lymphocytes ,Multiple Sclerosis ,Regulatory T cell ,T cell ,Immunology ,Biology ,Epigenesis, Genetic ,Arthritis, Rheumatoid ,TCIRG1 ,03 medical and health sciences ,Interleukin 21 ,Th2 Cells ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Cell Lineage ,IL-2 receptor ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Gene Expression Profiling ,Interleukin-17 ,DNA Methylation ,Th1 Cells ,3. Good health ,Cell biology ,medicine.anatomical_structure ,DNA methylation ,Cytokines ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Proper transcriptional control of pro- and anti-inflammatory responses of the immune system is important for a fine-tuned balance between protection and tolerance. Emerging evidence suggests a key role for epigenetic regulation in governing the Th cell differentiation, where effector cytokines direct the overall immune response. In this study, we describe a method to pinpoint the location of isolated human CD4+ T cells on any T cell effector axis based on specific CpG methylation of cytokine and transcription factor loci. We apply the method on CD4+ cells obtained from rheumatoid arthritis and multiple sclerosis patients and show that synovial fluid infiltrating CD4+ T cells are committed toward both Th1 and regulatory T cell phenotype, whereas the Th2 response is suppressed. Furthermore, we show that the IL-17A gene is regulated by promoter methylation and that Th17 commitment is not a common feature in the inflamed joints of rheumatoid arthritis patients. We conclude that the method described in this paper allows for accurate profiling of Th lineage commitment in ex vivo-isolated CD4+ T cells.
- Published
- 2011
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10. CCR2 upregulated on peripheral T cells in osteoarthritis but not in bone marrow
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Anders Enocson, Per Marits, Ola Winqvist, Kurt Arkestål, Hans Glise, Ludvig Linton, Michael Mints, and John Andersson
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,CCR2 ,Receptors, CXCR3 ,Receptors, CCR2 ,Joint replacement ,medicine.medical_treatment ,Immunology ,Bone Marrow Cells ,Cell Separation ,Osteoarthritis ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Immunophenotyping ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Humans ,Cells, Cultured ,Blood Cells ,business.industry ,Cell Differentiation ,General Medicine ,Flow Cytometry ,medicine.disease ,Up-Regulation ,Peripheral ,030104 developmental biology ,medicine.anatomical_structure ,Etiology ,Bone marrow ,business - Abstract
Osteoarthritis (OA) is a condition affecting millions of patients around the world, causing pain and disability and often resulting in joint replacement surgery. The aetiology of OA has long been attributed to mechanical wear mainly due to the increased prevalence of OA in load bearing joints among older patients. However, recent studies reveal a complex molecular disease causality in which inflammation, nutritional deficit and angiogenesis lead to the destruction of the joint structure. The aim of this study was to examine chemokine receptor expression in peripheral blood and bone marrow in OA patients. We devised a protocol for extracting healthy bone marrow from patients undergoing hip arthroplasty due to coxarthrosis. Flow cytometry was used to determine the expression of 18 chemokine receptors on CD4 and CD8 T cells from bone marrow and blood from 7 osteoarthritis patients and peripheral blood from 9 healthy controls. We found a significantly increased fraction of CCR2 expressing CD4 and CD8 T cell in peripheral blood compared to healthy controls. Also, there was a significant decrease in CXCR3 (Th1) (P 0.01) expressing T cells in peripheral blood from OA patients. Finally, multivariate analysis was used to separate T cell profiles from healthy controls and OA patients and demonstrate that the divergence of chemokine receptor expression occurs in the mature T cell subsets. In conclusion, we find increased CCR2 expression in peripheral blood from OA patients that possibly may be targeted in future clinical studies.
- Published
- 2018
11. Randomized, double-blind, placebo-controlled trial of CCR9-targeted leukapheresis treatment of ulcerative colitis patients
- Author
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Michael Eberhardson, Ludvig Linton, Hans Glise, Annelie Lindberg, Martina Jones Kostalla, Anders Odén, Per Karlén, Emma Lindh, Petra Jones, and Ola Winqvist
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Chemokine ,Placebo-controlled study ,Blood volume ,Placebo ,Gastroenterology ,Receptors, CCR ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Leukapheresis ,biology ,business.industry ,Monocyte ,General Medicine ,Flow Cytometry ,medicine.disease ,Ulcerative colitis ,Surgery ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Tolerability ,biology.protein ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,business - Abstract
Background and Aims: Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-alpha. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response. Methods: Patients with ulcerative colitis were treated every second day with leukapheresis during five sessions with a C-C chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column. Results: No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group [p = 0.0391] whereas no statistically significant change was seen in the placebo group [p = 0.4688]. There was a significant decrease of HLA-DRhi monocytes in the active group compared with the placebo group when corrected for the imbalance in weight between the groups [p = 0.0105]. Mayo score decreased in the active group [p = 0.0156] whereas the change in the placebo group was not significant [p = 0.1250]. Mayo score = 3 was observed in five out of 14 patients [35.7%] in the active group compared with one out of eight [12.5%] receiving placebo. The number of responders in the active treatment group was eight out of 14 patients [57.1%], whereas in the corresponding placebo group three out of eight patients [37.5%] responded to placebo. A dose-response correlation was observed between the blood volume processed and clinical outcome. Conclusion: This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.
- Published
- 2016
12. HLA-DR(hi) and CCR9 Define a Pro-Inflammatory Monocyte Subset in IBD
- Author
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Jeanette Grundström, Michael Eberhardson, Emma Lindh, Izabella Janczewska, Annelie Lindberg, Hans Glise, Per Karlén, Eric Hjalmarsson, Ola Winqvist, Ludvig Linton, Ragnar Befrits, and Mats Karlsson
- Subjects
business.industry ,Inflammatory Bowel Disease ,Gastroenterology ,CCR9 ,Inflammatory monocyte ,Human leukocyte antigen ,medicine.disease ,Bioinformatics ,Inflammatory bowel disease ,Phenotype ,digestive system diseases ,Intestinal mucosa ,Intestinal inflammation ,Immunology ,medicine ,In patient ,business - Abstract
OBJECTIVES: It has been demonstrated that circulating monocytes relocate to the intestinal mucosa during intestinal inflammation, but the phenotype and inflammatory mechanisms of these monocytes remain poorly understood. Here, we have investigated blood monocytes expressing high levels of HLA-DR and CCR9 in patients with inflammatory bowel disease (IBD). METHODS: Fifty-one patients with mild to severe ulcerative colitis (UC; n=31; UC-DAI 3–12) or Crohn's disease (CD; n=20; Harvey–Bradshaw indices (HBI) 2–16) were included together with 14 controls, during IBD therapy for four consecutive weeks. The frequency of CD14+HLA-DRhi monocytes was monitored weekly in peripheral blood, using flow cytometry. The surface phenotype and cytokine profile of these monocytes were established using flow cytometry and real-time PCR. Clinical parameters were assessed weekly in all patients. RESULTS: The frequency of circulating CD14+HLA-DRhi monocytes was significantly higher in IBD patients with moderate to severe disease compared with healthy controls (P
- Published
- 2012
13. Altered immunoregulatory profile during anti-tumour necrosis factor treatment of patients with inflammatory bowel disease
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Jeanette Grundström, H. Forsslund, Guro Gafvelin, Izabella Janczewska, Sarah Thunberg, Ludvig Linton, M. van Hage, Michael Eberhardson, and Ragnar Befrits
- Subjects
Male ,Regulatory T cell ,Immunology ,Anti-Inflammatory Agents ,Lymphocyte Activation ,Peripheral blood mononuclear cell ,T-Lymphocytes, Regulatory ,Interleukin 21 ,Intestinal mucosa ,medicine ,Immunology and Allergy ,Humans ,IL-2 receptor ,Antigens ,Intestinal Mucosa ,business.industry ,Interleukin ,FOXP3 ,Antibodies, Monoclonal ,T-Lymphocytes, Helper-Inducer ,Original Articles ,Inflammatory Bowel Diseases ,medicine.anatomical_structure ,Leukocytes, Mononuclear ,Tumor necrosis factor alpha ,Female ,Tumor Necrosis Factor Inhibitors ,business - Abstract
Summary Inflammatory bowel disease (IBD) can be treated effectively by anti-tumour necrosis factor (TNF) therapy. We set out to investigate the unclear immunoregulatory mechanisms of the treatment. Thirty-four patients with IBD treated with anti-TNF were included. Lymphocytes from peripheral blood and intestinal biopsies were analysed by flow cytometry. Regulation of antigen-stimulated proliferation was analysed by blocking of interleukin (IL)-10, transforming growth factor (TGF)-β or depletion of CD25+ cells in peripheral blood mononuclear cell cultures. No changes in CD4+CD25+, CD25+TNF-RII+ or CD4+CD25+forkhead box protein 3 (FoxP3+) T cells could be observed in peripheral blood after, in comparison to before, 6 weeks of treatment. The suppressive ability of CD4+CD25+ cells did not change. There was an initial decrease of CD4+CD25+ cells in intestinal mucosa after 2 weeks of treatment, followed by an increase of these cells from weeks 2 to 6 of treatment (P
- Published
- 2012
14. Naïve T cells in the gut: how to really find them?
- Author
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Michael Eberhardson, Ragnar Befrits, Izabella Janczewska, Maria Lampinen, Marie Carlson, Ola Winqvist, Mats Karlsson, Per Karlén, Hans Glise, and Ludvig Linton
- Subjects
Male ,Wound Healing ,Crohn Disease ,business.industry ,Immunology ,Gastroenterology ,Humans ,Medicine ,Colitis, Ulcerative ,Female ,T-Lymphocytes, Helper-Inducer ,Intestinal Mucosa ,business - Published
- 2014
15. CCR9-expressing CD14+HLA-DRhi blood monocytes promote intestinal inflammation in IBD
- Author
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Jeanette Grundström, Per Marits, Mats Karlsson, Per Karlén, Ola Winqvist, Annelie Lindberg, Michael Eberhardson, and Ludvig Linton
- Subjects
Medicine(all) ,Veterinary medicine ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,CD14 ,CCR9 ,General Medicine ,Human leukocyte antigen ,General Biochemistry, Genetics and Molecular Biology ,Intestinal inflammation ,Immunology ,Poster Presentation ,Medicine ,business - Full Text
- View/download PDF
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