scholarly journals Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia

2018 ◽  
Vol 132 (3) ◽  
pp. 419-436 ◽  
Author(s):  
Sabrina M. Scroggins ◽  
Donna A. Santillan ◽  
Jenna M. Lund ◽  
Jeremy A. Sandgren ◽  
Lindsay K. Krotz ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Maternal Plasma ◽  
Hypertensive Disorder ◽  
Wild Type ◽  
T Helper ◽  
Anti Inflammatory ◽  
Immune Changes ◽  
Anti Inflammatory Cytokine

The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE. AVP infusion throughout gestation in mice resulted in increased pro-inflammatory interferon γ (IFNg) (TH1) in the maternal plasma. The TH17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the TH2-associated anti-inflammatory cytokine IL-4 was decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10 was decreased in the maternal kidney and all fetal tissues. Collectively, these results demonstrate the sufficiency of AVP to induce the immune changes typical of PreE. We investigated if T cells can respond directly to AVP by evaluating the expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was decreased in CD4+ T cells obtained from PreE-affected women. In total, our data are consistent with a potential initiating role for AVP in the immune dysfunction typical of PreE and identifies putative signaling mechanism(s) for future investigation.

Abrogation of Donor T Cell IL-21 Signaling Leads to Tissue-Specific Modulation of Immunity and Separation of Gvhd From GVL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 729-729
Author(s):  
Alan M. Hanash ◽  
Lucy W. Kappel ◽  
Nury L. Yim ◽  
Rebecca A. Nejat ◽  
Gabrielle L. Goldberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Wild Type ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Donor T Cells

Abstract Abstract 729 Allogeneic hematopoietic transplantation is frequently the only curative therapy available to patients with hematopoietic malignancies, however transplant success continues to be limited by complications including graft vs. host disease (GVHD) and disease relapse. Separation of GVHD from graft vs. leukemia/lymphoma (GVL) responses continues to be a major goal of experimental and clinical transplantation, and better understanding of T cell immunobiology may lead to novel strategies to accomplish this goal. Interleukin 21 (IL-21) is a pro-inflammatory cytokine produced by Th17 helper T cells, and abrogation of IL-21 signaling has recently been demonstrated to reduce GVHD while retaining GVL. However, the mechanisms by which IL-21 may lead to a separation of GVHD and GVL are incompletely understood. In order to characterize the effect of IL-21 on GVH and GVL T cell responses, we compared wild type and IL-21 receptor knockout (IL-21R KO) donor T cells in a C57BL/6 into BALB/c murine MHC-mismatched bone marrow transplant (BMT) model. Lethally irradiated BMT recipients of IL-21R KO T cells demonstrated decreased GVHD-related morbidity (p<.05) and mortality (p<.01), and decreased histopathologic evidence of GVHD within the small intestine (p<.05). While this reduction in IL-21R KO T cell-mediated GVHD was associated with increased donor regulatory T cells two to three weeks post-BMT (p<.001), IL-21 signaling in both donor CD4 and donor CD8 T cells was found to contribute to GVHD mortality (p<.01 for CD4, p<.05 for CD8). Analysis of IL-21R expression by wild type T cells demonstrated receptor upregulation upon polyclonal activation in vitro and upon alloactivation in vivo (p<.01). However, this IL-21R upregulation was not required for in vivo alloactivation, as IL-21R KO and wild type donor T cells demonstrated equivalently greater proliferation in allogeneic vs. syngeneic recipients (p<.001), equivalent upregulation of CD25 (p<.001), and equivalent downregulation of CD62L (p<.01 for CD8 T cells). Despite this equivalent alloactivation, IL-21R KO T cells demonstrated decreased infiltration within the small intestine (p<.05), decreased infiltration in mesenteric lymph nodes (p<.05 for CD8 T cells, p<.001 for CD4 T cells), and decreased inflammatory cytokine-producing CD4 T cells within mesenteric lymph nodes (p<.01 for IFN-g, p<.001 for TNF-a, Figure 1A). Consistent with this, transplanted IL-21R KO donor T cells demonstrated decreased expression of a4b7 integrin (LPAM, p<.05), a molecule known to be involved in homing of GVHD-mediating donor T cells to the gut. However, in contrast to the reduced inflammatory cytokine-producing CD4 T cells observed in mesenteric lymph nodes, IL-21R KO helper T cell cytokine production was maintained in spleen (Figure 1B) and peripheral lymph nodes, and IL-21R KO T cells were able to protect recipient mice from lethality due to A20 lymphoma (p<.001). In summary, abrogation of IL-21 signaling in donor T cells leads to tissue-specific modulation of immunity, such that gastrointestinal GVHD is reduced, but peripheral T cell function and GVL capacity are retained. Targeting IL-21 for therapeutic intervention is an exciting strategy to separate GVHD from GVL, and this novel approach should be considered for clinical investigation to improve transplant outcomes and prevent malignant relapse. Disclosures: No relevant conflicts of interest to declare.

T cells producing the anti-inflammatory cytokine IL-10 regulate allergen-specific Th2 responses in human airways

Allergy ◽  
2012 ◽  
Vol 67 (8) ◽  
pp. 1007-1013 ◽  
Author(s):  
A. Faith ◽  
N. Singh ◽  
S. Farooque ◽  
S. Dimeloe ◽  
D. F. Richards ◽  
...  
Keyword(s):  
T Cells ◽  
Inflammatory Cytokine ◽  
Th2 Responses ◽  
Anti Inflammatory ◽  
Human Airways ◽  
Anti Inflammatory Cytokine

IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis

2017 ◽  
Vol 114 (1) ◽  
pp. 180-187 ◽  
Author(s):  
Daniel Engelbertsen ◽  
Sara Rattik ◽  
Maria Wigren ◽  
Jenifer Vallejo ◽  
Goran Marinkovic ◽  
...  
Keyword(s):  
T Cells ◽  
High Fat Diet ◽  
Cd4 T Cells ◽  
Wild Type ◽  
T Helper ◽  
High Fat ◽  
Lesion Development ◽  
Ifn Γ

Abstract Aims The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. Methods and results We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. Conclusion We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.

scholarly journals Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro

2019 ◽  
Vol 33 ◽  
pp. 205873841984493
Author(s):  
Mamdooh H Ghoneum ◽  
James K Gimzewski ◽  
Aya D Ghoneum ◽  
Sudhanshu Agrawal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Assay ◽  
Iron Based ◽  
Anti Inflammatory ◽  
Human Dendritic Cells

The hydroferrate fluid MRN-100, an iron-based compound with potent antioxidant characteristics, was examined to identify its possible anti-inflammatory effects on human dendritic cells (DCs) in vitro. Human monocyte–derived DCs were treated with MRN-100 at two concentrations (50 and 100 μL/mL) for 24 h and then stimulated with or without lipopolysaccharides (LPS). The expression of DC maturation markers was assessed by flow cytometry and the production of cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Functional assay was performed by co-culturing MRN-100-treated and untreated DCs with allogeneic naïve CD4+ T cells and assaying the T cells’ cytokine production. Results show that treatment with MRN-100 significantly upregulated the co-stimulatory molecules CD80 and CD86 and increased human leukocyte antigen-DR (HLA-DR) though not significantly. MRN-100 treatment also significantly increased the production of the anti-inflammatory cytokine interleukin (IL)-10. On the other hand, MRN-100 significantly induced the secretion of pro-inflammatory cytokines such as IL-6 only at high concentrations. Furthermore, DCs pretreated with MRN-100 and either stimulated or not with LPS were able to prime CD4+ T cells to secrete significant amounts of IL-10 while inhibiting the secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-α. These results indicate that MRN-100 is a powerful anti-inflammatory agent that promotes the generation of an anti-inflammatory immune response in vitro. MRN-100 could be beneficial for treating patients with inflammatory diseases, including arthritis and type 1 diabetes, and its potential benefits should be examined in clinical trials.

Interleukin-19 as an Immunoregulatory Cytokine

2020 ◽  
Vol 14 (2) ◽  
pp. 191-199
Author(s):  
Yasuyuki Fujimoto ◽  
Nobuyuki Kuramoto ◽  
Masanori Yoneyama ◽  
Yasu-Taka Azuma
Keyword(s):  
T Cells ◽  
Inflammatory Cytokine ◽  
The Other ◽  
Acquired Immunity ◽  
Current Role ◽  
Immunoregulatory Cytokine ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Inflammatory Effect

IL-19 is a type of anti-inflammatory cytokine. Since the receptor for IL-19 is common to IL-20 and IL-24, it is important to clarify the role of each of the three cytokines. If three different cytokines bind to the same receptor, these three may have been produced to complement the other two. However, perhaps it is unlikely. Recently, the existence of a novel receptor for IL-19 was suggested. The distinction between the roles of the three cytokines still makes sense. On the other hand, because T cells do not produce IL-19, their role in acquired immunity is limited or indirect. It has been reported that IL-19 causes inflammation in some diseases but does not have an anti-inflammatory effect. In this review, we introduce the current role of IL-19 in each disease. In addition, we will describe the molecular mechanism of IL-19 and its development for the prevention of diseases. IL-19 was previously considered an anti-inflammatory cytokine, but we would like to propose it as an immunoregulatory cytokine.

Male fetal sex is associated with low maternal plasma anti-inflammatory cytokine profile in the first trimester of healthy pregnancies

Cytokine ◽  
2020 ◽  
Vol 136 ◽  
pp. 155290
Author(s):  
David Ramiro-Cortijo ◽  
María de la Calle ◽  
Rainer Böger ◽  
Juliane Hannemann ◽  
Nicole Lüneburg ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
First Trimester ◽  
Maternal Plasma ◽  
Cytokine Profile ◽  
Fetal Sex ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine
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