Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease

Objective.To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF–driven Th17 cell differentiation.Methods.Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured. CD4+CD25− T cells and monocytes were purified from the blood of healthy donors and cocultured in the presence of anti-CD3, with or without etanercept (ETN), eicosapentaenoic acid (EPA), or the control fatty acid, linoleic acid (LA). Expression of interleukin 17 and interferon-γ was measured by intracellular staining and flow cytometry.Results.Plasma PC EPA levels and the EPA/arachidonic acid ratio correlated inversely with change in the Disease Activity Score at 28 joints (DAS28) at 3 months (−0.51, p = 0.007 and −0.48, p = 0.01, respectively), indicating that higher plasma EPA was associated with a greater reduction in DAS28. Plasma PC EPA was positively associated with European League Against Rheumatism response (p = 0.02). An increase in Th17 cells post-therapy has been associated with nonresponse to anti-TNF. ETN increased Th17 frequenciesin vitro. Physiological concentrations of EPA, but not LA, prevented this.Conclusion.EPA status was associated with clinical improvements to anti-TNF therapyin vivoand prevented the effect of ETN on Th17 cellsin vitro. EPA supplementation might be a simple way to improve anti-TNF outcomes in patients with RA by suppressing Th17 frequencies.

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CD49d provides access to “untouched” human Foxp3+ Treg free of contaminating effector cells

Blood ◽

10.1182/blood-2008-04-150524 ◽

2009 ◽

Vol 113 (4) ◽

pp. 827-836 ◽

Cited By ~ 92

Author(s):

Markus Kleinewietfeld ◽

Mireille Starke ◽

Diletta Di Mitri ◽

Giovanna Borsellino ◽

Luca Battistini ◽

...

Keyword(s):

Mononuclear Cells ◽

Treg Cells ◽

Interferon Γ ◽

Clinical Applications ◽

Interleukin 17 ◽

Peripheral Blood Mononuclear ◽

Effector Cells ◽

Ifn Γ

Abstract The adoptive transfer of regulatory Foxp3+ T (Treg) cells has been shown in various animal models to prevent inflammatory immune and autoimmune diseases. Translation into therapeutic applications, however, is hindered by the lack of suitable techniques and markers. CD25, commonly used to isolate Treg cells from mice, has only limited value in humans as it is also present on proinflammatory CD4+ effector cells. Here we show that clean populations of human Foxp3+ Treg cells can be obtained with antibodies directed against CD49d. The marker is present on proinflammatory peripheral blood mononuclear cells but is absent on immune-suppressive Treg cells. Depletion with α-CD49d removes contaminating interferon-γ (IFN-γ)– and interleukin-17 (IL-17)–secreting cells from Treg preparations of CD4+CD25high cells. More importantly, in combination with α-CD127 it allows the isolation of “untouched” Foxp3+ Treg (ie, cells that have not been targeted by an antibody during purification). The removal of CD49d+/CD127+ cells leaves a population of Foxp3+ Treg virtually free of contaminating CD25+ effector cells. The cells can be expanded in vitro and are effective suppressors both in vitro and in vivo. Thus, CD49d provides access to highly pure populations of untouched Foxp3+ Treg cells conferring maximal safety for future clinical applications.

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Rapidly expanded partially HLA DRB1–matched fungus-specific T cells mediate in vitro and in vivo antifungal activity

Blood Advances ◽

10.1182/bloodadvances.2020001565 ◽

2020 ◽

Vol 4 (14) ◽

pp. 3443-3456

Author(s):

Gloria Castellano-González ◽

Helen M. McGuire ◽

Fabio Luciani ◽

Leighton E. Clancy ◽

Ziduo Li ◽

...

Keyword(s):

T Cells ◽

Fungal Infection ◽

Fungal Infections ◽

Interferon Γ ◽

Third Party ◽

Interleukin 17 ◽

Cell Transplant ◽

Hematopoietic Stem

Abstract Invasive fungal infections are a major cause of disease and death in immunocompromised hosts, including patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Recovery of adaptive immunity after HSCT correlates strongly with recovery from fungal infection. Using initial selection of lymphocytes expressing the activation marker CD137 after fungal stimulation, we rapidly expanded a population of mainly CD4+ T cells with potent antifungal characteristics, including production of tumor necrosis factor α, interferon γ, interleukin-17, and granulocyte-macrophage colony stimulating factor. Cells were manufactured using a fully good manufacturing practice–compliant process. In vitro, the T cells responded to fungal antigens presented on fully and partially HLA-DRB1 antigen–matched presenting cells, including when the single common DRB1 antigen was allelically mismatched. Administration of antifungal T cells lead to reduction in the severity of pulmonary and cerebral infection in an experimental mouse model of Aspergillus. These data support the establishment of a bank of cryopreserved fungus-specific T cells using normal donors with common HLA DRB1 molecules and testing of partially HLA-matched third-party donor fungus-specific T cells as a potential therapeutic in patients with invasive fungal infection after HSCT.

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CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunity

Journal of Experimental Medicine ◽

10.1084/jem.20102010 ◽

2011 ◽

Vol 208 (2) ◽

pp. 327-339 ◽

Cited By ~ 141

Author(s):

Lillian Cruz-Orengo ◽

David W. Holman ◽

Denise Dorsey ◽

Liang Zhou ◽

Penglie Zhang ◽

...

Keyword(s):

Interferon Γ ◽

Interleukin 17 ◽

Leukocyte Infiltration ◽

Brain Endothelial Cells ◽

Autoimmune Encephalomyelitis ◽

Inflammatory Infiltration ◽

Endothelial Barriers ◽

The Central Nervous System ◽

Experimental Autoimmune

Loss of CXCL12, a leukocyte localizing cue, from abluminal surfaces of the blood–brain barrier occurs in multiple sclerosis (MS) lesions. However, the mechanisms and consequences of reduced abluminal CXCL12 abundance remain unclear. Here, we show that activation of CXCR7, which scavenges CXCL12, is essential for leukocyte entry via endothelial barriers into the central nervous system (CNS) parenchyma during experimental autoimmune encephalomyelitis (EAE), a model for MS. CXCR7 expression on endothelial barriers increased during EAE at sites of inflammatory infiltration. Treatment with a CXCR7 antagonist ameliorated EAE, reduced leukocyte infiltration into the CNS parenchyma and parenchymal VCAM-1 expression, and increased abluminal levels of CXCL12. Interleukin 17 and interleukin 1β increased, whereas interferon-γ decreased, CXCR7 expression on and CXCL12 internalization in primary brain endothelial cells in vitro. These findings identify molecular requirements for the transvascular entry of leukocytes into the CNS and suggest that CXCR7 blockade may have therapeutic utility for the treatment of MS.

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Curcumin mediates attenuation of pro-inflammatory interferon γ and interleukin 17 cytokine responses in psoriatic disease, strengthening its role as a dietary immunosuppressant

Nutrition Research ◽

10.1016/j.nutres.2020.01.005 ◽

2020 ◽

Vol 75 ◽

pp. 95-108 ◽

Cited By ~ 3

Author(s):

Dimitrios Ν. Skyvalidas ◽

Athanasios Mavropoulos ◽

Sotirios Tsiogkas ◽

Efthymios Dardiotis ◽

Christos Liaskos ◽

...

Keyword(s):

Interferon Γ ◽

Interleukin 17 ◽

Psoriatic Disease ◽

Cytokine Responses

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Type 17 CD8+ T cells display enhanced antitumor immunity

Blood ◽

10.1182/blood-2009-02-203935 ◽

2009 ◽

Vol 114 (3) ◽

pp. 596-599 ◽

Cited By ~ 147

Author(s):

Christian S. Hinrichs ◽

Andrew Kaiser ◽

Chrystal M. Paulos ◽

Lydie Cassard ◽

Luis Sanchez-Perez ◽

...

Keyword(s):

T Cells ◽

Cancer Therapy ◽

Cd8 T Cells ◽

Antitumor Immunity ◽

Killer Cell ◽

Cd8 T Cell ◽

Interferon Γ ◽

Interleukin 17 ◽

Effector Cells

Abstract Interleukin-17 (IL-17)–secreting CD8+ T cells have been described, but they have not been thoroughly studied and they do not have a known role in cancer immunotherapy. We skewed CD8+ T cells to secrete IL-17 through priming in Th17-polarizing conditions. IL-17–producing CD8+ T cells demonstrated reduced expression of Eomes and diminished cytolytic differentiation in vitro. However, after adoptive transfer, these cells converted to interferon-γ–producing effector cells and mediated regression of large, established tumors. This improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells. This report is the first description of a cancer therapy with IL-17–secreting CD8+ T cells. These findings have implications for the improvement of CD8+ T cell–based adoptive immunotherapy.

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Murine brain endothelial cells differently modulate interferon-γ and interleukin-17 production in vitro

Archives of Biological Sciences ◽

10.2298/abs0901029m ◽

2009 ◽

Vol 61 (1) ◽

pp. 29-36

Author(s):

Miljana Momcilovic ◽

D. Miljkovic ◽

Marija Mostarica-Stojkovic

Keyword(s):

Endothelial Cells ◽

Immune Cells ◽

Interferon Γ ◽

Interleukin 17 ◽

Brain Endothelial Cell ◽

Brain Endothelial Cells ◽

Cns Inflammation ◽

Lymph Node Cells ◽

Pro Inflammatory Cytokines

Brain endothelial cells (BEC) are the major constituents of the blood-brain barrier (BBB), the structure that controls entrance of immune cells into CNS parenchyma. Our aim was to investigate the influence of BEC on production of IL-17 and IFN-?-cytokines that are important for CNS inflammation. To that end, co-cultivations of the bEnd.3 brain endothelial cell line and lymph node cells (LNC) were performed, and gene expression and production of IL-17 and IFN-? were determined. It was found that bEnd.3 cells inhibited expression and production of IFN-?, but not of IL-17. Additionally, bEnd.3 cells also reduced production of the major IFN-?-promoting cytokine - IL-12 - in LNC. The observed variation in modulation of pro-inflammatory cytokines by BEC could be of importance for the understanding of CNS inflammation.

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Levels interleukine-4 and interleukin-17 (IL-4, IL-17) of blood in patients with habitual recurrent pregnancy loss, which occurred in a loop in vitro fertilization

HEALTH OF WOMAN ◽

10.15574/hw.2016.114.137 ◽

2016 ◽

pp. 137-139

Author(s):

K.P. Golovatyuk ◽

Keyword(s):

In Vitro Fertilization ◽

Conditioned Medium ◽

Mononuclear Cells ◽

Recurrent Miscarriage ◽

Interleukin 4 ◽

Control Group ◽

Interleukin 17 ◽

Vitro Fertilization ◽

Blood Mononuclear Cells

The objective: was to investigate the levels of cytokines IL-4 and IL-17 in serum and conditioned medium cultures of blood mononuclear cells (MNC) and evaluation association between their products and miscarriage, which occurred in IVF cycles. Patients and methods. We observed 240 patients with recurrent miscarriage, came in IVF cycles, and 100 apparently healthy fertile women in the control group. The concentrations of IL-4 and IL-17 in serum and conditioned medium of MNC cultures were determined. Results. The levels of IL-4 in the serum and conditioned medium in spontaneous and stimulated mitogen secretion was not significantly different from those in the control group, whereas IL-17 levels were higher than those in the control group serum, in conditioned media of stimulated and non-stimulated MNCs. Conclusion. Disregulation of activity of circulating blood mononuclear cells in women with recurrent miscarriage that followed IVF, is accompanied by increased secretion of IL-17 and almost constant production of IL-4 on the back of high stimulation index of production of these cytokines. Key words: in vitro fertilization, miscarriage, interleukin-4, interleukin-17, serum stimulated and non-stimulated mononuclear blood.

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