scholarly journals The endometrial immune environment of women with endometriosis

2019 ◽  
Vol 25 (5) ◽  
pp. 565-592 ◽  
Author(s):  
Júlia Vallvé-Juanico ◽  
Sahar Houshdaran ◽  
Linda C Giudice
Keyword(s):  
T Cells ◽  
Immune System ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Immune Cell ◽  
Reproductive Age ◽  
Cycle Phase ◽  
Cell Populations ◽  
Killer Cells

Abstract BACKGROUND Endometriosis, a common oestrogen-dependent inflammatory disorder in women of reproductive age, is characterized by endometrial-like tissue outside its normal location in the uterus, which causes pelvic scarring, pain and infertility. While its pathogenesis is poorly understood, the immune system (systemically and locally in endometrium, pelvic endometriotic lesions and peritoneal fluid) is believed to play a central role in its aetiology, pathophysiology and associated morbidities of pain, infertility and poor pregnancy outcomes. However, immune cell populations within the endometrium of women with the disease have had incomplete phenotyping, thereby limiting insight into their roles in this disorder. OBJECTIVE AND RATIONALE The objective herein was to determine reproducible and consistent findings regarding specific immune cell populations and their abundance, steroid hormone responsiveness, functionality, activation states, and markers, locally and systemically in women with and without endometriosis. SEARCH METHODS A comprehensive English language PubMed, Medline and Google Scholar search was conducted with key search terms that included endometriosis, inflammation, human eutopic/ectopic endometrium, immune cells, immune population, immune system, macrophages, dendritic cells (DC), natural killer cells, mast cells, eosinophils, neutrophils, B cells and T cells. OUTCOMES In women with endometriosis compared to those without endometriosis, some endometrial immune cells display similar cycle-phase variation, whereas macrophages (Mø), immature DC and regulatory T cells behave differently. A pro-inflammatory Mø1 phenotype versus anti-inflammatory Mø2 phenotype predominates and natural killer cells display abnormal activity in endometrium of women with the disease. Conflicting data largely derive from small studies, variably defined hormonal milieu and different experimental approaches and technologies. WIDER IMPLICATIONS Phenotyping immune cell subtypes is essential to determine the role of the endometrial immune niche in pregnancy and endometrial homeostasis normally and in women with poor reproductive history and can facilitate development of innovative diagnostics and therapeutics for associated symptoms and compromised reproductive outcomes.

scholarly journals Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors

2019 ◽  
Vol 29 (9) ◽  
pp. 1381-1388 ◽  
Author(s):  
An Coosemans ◽  
Thaïs Baert ◽  
Jolien Ceusters ◽  
Pieter Busschaert ◽  
Chiara Landolfo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune System ◽  
Natural Killer Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Killer Cells

BackgroundThe behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.MethodsIn this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.ResultsIn a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.ConclusionsOur immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

scholarly journals Lymphocytes and Trogocytosis-Mediated Signaling

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1478
Author(s):  
Jim Reed ◽  
Madison Reichelt ◽  
Scott A. Wetzel
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Intracellular Signaling ◽  
Immune Cell ◽  
Nk Cell ◽  
Γδ T Cells ◽  
Killer Cells ◽  
The Individual ◽  
The Impact

Trogocytosis is the intercellular transfer of membrane and membrane-associated molecules. This underappreciated process has been described in a variety of biological settings including neuronal remodeling, fertilization, viral and bacterial spread, and cancer, but has been most widely studied in cells of the immune system. Trogocytosis is performed by multiple immune cell types, including basophils, macrophages, dendritic cells, neutrophils, natural killer cells, B cells, γδ T cells, and CD4+ and CD8+ αβ T cells. Although not expressed endogenously, the presence of trogocytosed molecules on cells has the potential to significantly impact an immune response and the biology of the individual trogocytosis-positive cell. Many studies have focused on the ability of the trogocytosis-positive cells to interact with other immune cells and modulate the function of responders. Less understood and arguably equally important is the impact of these molecules on the individual trogocytosis-positive cell. Molecules that have been reported to be trogocytosed by cells include cognate ligands for receptors on the individual cell, such as activating NK cell ligands and MHC:peptide. These trogocytosed molecules have been shown to interact with receptors on the trogocytosis-positive cell and mediate intracellular signaling. In this review, we discuss the impact of this trogocytosis-mediated signaling on the biology of the individual trogocytosis-positive cell by focusing on natural killer cells and CD4+ T lymphocytes.

scholarly journals Effect of combined contraceptive pill on immune cell of ovarian endometriotic tissue

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Wanwisa Waiyaput ◽  
Keerati Wattanakamolchai ◽  
Yada Tingthanatikul ◽  
Srithean Lertvikool ◽  
Siriluk Tantanavipas ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Cyst Wall ◽  
Immune Cell ◽  
Ethinyl Estradiol ◽  
Untreated Group ◽  
Killer Cells ◽  
Endometriotic Cyst

Abstract Background Dysregulation of immune response is associated with development of endometriosis. The study aim was to evaluate effect of combined oral contraceptive pills (COCs) consisting of ethinyl estradiol (EE) and desogestrel on the expression of macrophage, natural killer cells, and regulatory T cells of ovarian endometriotic cysts. Methods Endometriotic cyst wall tissues were collected from women with endometriosis who were treated (n = 22) with COCs (one table per day of EE 0.03 mg and desogestrel 0.15 mg administered for 28 to 35 days before surgery) or untreated (n = 22). The tissues were collected from endometriotic cyst wall during laparoscopic or laparotomy ovarian cystectomy. Immunohistochemistry for anti-CD68, anti-CD56, and anti-forkhead–winged helix transcription factor (FoxP3), a marker for macrophages, natural killer cells, and regulatory T cells, respectively, were investigated. Results The median (interquartile range [IQR]) number of anti-CD68 positive cells in the COC group was significantly lower than in the untreated group (12.7; 4.9–19.3) versus 45.7 (26.0–70.7), p < 0.001). Tissue infiltration of anti-CD56 positive cells in endometriotic cyst was significantly higher after the treatment when compared with tissue from untreated group (42.9, 27.4–68.9 versus 25.3 (14.1–37.3; p = 0.009). The number of regulatory T cells was also significantly increased in the COC group (6.3, 2.8–15.5) versus 0 (0–1.8; p < 0.001). Conclusions The effects of COC, containing EE 0.30 mg with desogestrel 0.15 mg, on the immune system was demonstrated by a significant decrease in the number of macrophages and an increase in natural killer and regulatory T cells.

scholarly journals Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joseph A. C. Delaney ◽  
Nels C. Olson ◽  
Colleen M. Sitlani ◽  
Alison E. Fohner ◽  
Sally A. Huber ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Natural Killer Cells ◽  
Systolic Blood Pressure ◽  
Natural Killer ◽  
Immune Cells ◽  
Immune Cell ◽  
Average Systolic Blood Pressure ◽  
Immune Cell Subsets ◽  
Classical Monocytes

Abstract Background Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP). Methods We assayed immune cells from cryopreserved samples collected at the baseline examination (2000–2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level. Results The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34–3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82–2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14++CD16−) was associated with 2.01 mmHG (95% CI 0.79–3.24) lower average systolic blood pressure. There were no associations of CD4+ T helper cell subsets with average systolic blood pressure. Conclusion These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

scholarly journals OP0023 GENERATION OF PT101, A HIGHLY SELECTIVE IL-2 MUTEIN FOR TREATMENT OF AUTOIMMUNE DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 13.1-13
Author(s):  
J. Visweswaraiah ◽  
E. Sampson ◽  
P. Petaipimol ◽  
A. Monsef ◽  
K. Kis-Toth ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Natural Killer Cells ◽  
Autoimmune Diseases ◽  
Natural Killer ◽  
Cytokine Production ◽  
Immune Cell ◽  
Cell Types ◽  
Killer Cells

Background:Regulatory T cells (Tregs) play a critical role in immune homeostasis and are dysfunctional in many autoimmune diseases. Interleukin 2 (IL-2) drives the proliferation and function of Tregs. via the heterotrimeric IL-2 receptor (CD25/CD122/CD132). As a result, CD25 loss-of-function in mice is associated with Treg deficiency and widespread autoimmunity. Low dose IL-2 is being evaluated for treatment of autoimmune diseases and has been shown to expand Tregs, however it has a narrow selectivity window before activating conventional T cells and natural killer cells. To enhance IL-2 selectivity and improve its therapeutic utility for activating and expanding Tregs, mutations can be introduced that reduce CD122/CD132 affinity thus creating a dependency on CD25 binding for signaling through CD122/CD132 upon IL-2 facilitated CD25/CD122/CD132 trimer formation.Objectives:To generate a highly selective IL-2 mutein that activates and expands Tregs selectively that can be used for treatment of autoimmune diseasesMethods:Using a structure guided approach, we introduced mutations in IL-2 that significantly decreased CD122 binding affinity in addition to other mutations that increased CD25 binding affinity. Finally, we explored additional mutations, format, orientation, and linker lengths to generate the most potent, selective molecule with drug-like manufacturability. These structure activity relationship efforts culminated in the generation of PT101, a mutant IL-2 Fc fusion that is selective in activating and expanding Tregs in vitro and in vivo.Results:PT101 selectively induced STAT5 phosphorylation in human and cynomolgus monkey Tregs in vitro. In humanized NOD-scid IL-2Rg-null (NSG) mice and cynomolgus monkeys, administration of PT101 dose-dependently and selectively expanded Tregs without significant effects on other immune cell types, and without eliciting proinflammatory cytokine production. The Tregs from PT101-dosed humanized mice have increased expression of FOXP3 and CD25, suggesting enhanced function and stability. In a Phase 1a single ascending dose clinical trial, PT101 was well-tolerated and selectively expanded total Tregs, with a mean maximal increase of up to 3.6-fold over baseline in healthy volunteers. There was no evidence of expansion of natural killer cells nor pro-inflammatory conventional T cells at any of the doses studied.Conclusion:PT101 selectively activated and expanded Tregs without significant effects on other immune cell types, and without eliciting proinflammatory cytokine production. These Tregs have enhanced function and stability as seen by increase in expression of FOXP3 and CD25 in these cells. PT101 maintained selectivity in Phase 1 a clinical trial with no evidence of expansion of natural killer cells nor pro-inflammatory conventional T at any dose studied. A Phase 1b/2a clinical trial in patients with ulcerative colitis and a Phase 2 clinical trial in patients with systemic lupus erythematosus are planned to further evaluate PT101.Disclosure of Interests:None declared

scholarly journals Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells

Nano Today ◽  
2021 ◽  
Vol 36 ◽  
pp. 101056
Author(s):  
Antonio Astorga-Gamaza ◽  
Michele Vitali ◽  
Mireya L. Borrajo ◽  
Rosa Suárez-López ◽  
Carlos Jaime ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Killer Cells ◽  
Cooperative Adsorption
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