Activation of the group 2 innate lymphoid cell (ILC2) population leads to production of the classical type 2 cytokines, thus promoting type 2 immunity. Chemoattractant receptor-homologous molecule ...expressed on TH2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2), is expressed by human ILC2s. However, the function of CRTH2 in these cells is unclear.
We sought to determine the role of PGD2 and CRTH2 in human ILC2s and compare it with that of the established ILC2 activators IL-25 and IL-33.
The effects of PGD2, IL-25, and IL-33 on the cell migration, cytokine production, gene regulation, and receptor expression of ILC2s were measured with chemotaxis, ELISA, Luminex, flow cytometry, quantitative RT-PCR, and QuantiGene assays. The effects of PGD2 under physiologic conditions were evaluated by using the supernatant from activated mast cells.
PGD2 binding to CRTH2 induced ILC2 migration and production of type 2 cytokines and many other cytokines. ILC2 activation through CRTH2 also upregulated the expression of IL-33 and IL-25 receptor subunits (ST2 and IL-17RA). The effects of PGD2 on ILC2s could be mimicked by the supernatant from activated human mast cells and inhibited by a CRTH2 antagonist.
PGD2 is an important and potent activator of ILC2s through CRTH2 mediating strong proallergic inflammatory responses. Through IgE-mediated mast cell degranulation, these innate cells can also contribute to adaptive type 2 immunity; thus CRTH2 bridges the innate and adaptive pathways in human ILC2s.
Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen ...challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.
Background Group 2 innate lymphoid cells (ILC2s) are a potential innate source of type 2 cytokines in the pathogenesis of allergic conditions. Epithelial cytokines (IL-33, IL-25, and thymic stromal ...lymphopoietin TSLP) and mast cell mediators (prostaglandin D2 PGD2 ) are critical activators of ILC2s. Cysteinyl leukotrienes (cysLTs), including leukotriene (LT) C4 , LTD4 , and LTE4 , are metabolites of arachidonic acid and mediate inflammatory responses. Their role in human ILC2s is still poorly understood. Objectives We sought to determine the role of cysLTs and their relationship with other ILC2 stimulators in the activation of human ILC2s. Methods For ex vivo studies, fresh blood from patients with atopic dermatitis and healthy control subjects was analyzed with flow cytometry. For in vitro studies, ILC2s were isolated and cultured. The effects of cysLTs, PGD2 , IL-33, IL-25, TSLP, and IL-2 alone or in combination on ILC2s were defined by using chemotaxis, apoptosis, ELISA, Luminex, quantitative RT-PCR, and flow cytometric assays. The effect of endogenous cysLTs was assessed by using human mast cell supernatants. Results Human ILC2s expressed the LT receptor CysLT1 , levels of which were increased in atopic subjects. CysLTs, particularly LTE4 , induced migration, reduced apoptosis, and promoted cytokine production in human ILC2s in vitro . LTE4 enhanced the effect of PGD2 , IL-25, IL-33, and TSLP, resulting in increased production of type 2 and other proinflammatory cytokines. The effect of LTE4 was inhibited by montelukast, a CysLT1 antagonist. Interestingly, addition of IL-2 to LTE4 and epithelial cytokines significantly amplified ILC2 activation and upregulated expression of the receptors for IL-33 and IL-25. Conclusion CysLTs, particularly LTE4 , are important contributors to the triggering of human ILC2s in inflammatory responses, particularly when combined with other ILC2 activators.
Innate lymphoid cells (ILC) are part of a heterogeneous family of haematopoietic effector cells which lack re-arranged antigen-specific receptors. They promote host defense and contribute to tissue ...and metabolic homeostasis, wound healing and immune surveillance. Their role in human cancer immunity is less defined, and therefore we aimed to identify the frequency and phenotype of distinct ILC groups in various types of cancer.
Tissue samples and peripheral blood were collected from patients undergoing surgical resection of gastrointestinal and breast tumours. Single cell suspension of tumour tissue was immediately obtained following surgery using tumour dissociation.
We observed significantly higher frequencies of ILC2 (p value: 0.04) in malignant breast cancer tissue and significantly higher frequencies of group 1 ILC (p value: 0.001) in malignant gastrointestinal tumours. Tumour infiltrating ILC were found to show an activated phenotype with higher expression of MHC-II, KLRG1, early activation marker CD69 and CD44.
Activated innate lymphoid cells infiltrate tumours dependent on tumour type and location.
Introduction Mild cognitive impairment (MCI) is a progressive age-related condition caused by physiological and structural changes in the brain, such as neurodegeneration and hypometabolism. ...Transcranial photobiomodulation (tPBM) is a neuromodulation technique that improves brain metabolism and oxygenation by irradiating red to near-infrared light on a specific area of the head. This study aimed to investigate the effect of multi-session tPBM on the cognitive capacities and attentional function of older women with MCI. Material and methods In this randomized controlled trial, 42 older women with MCI were randomly assigned to 2 equal groups: real and sham. The mini-mental state examination (MMSE) and the attentional Go/No-Go task were used to examine the patients. On the right frontal-pole of the cortex, 5 sessions of 850 nm tPBM were given. Re-examinations were conducted on the participants. For the Go/No-Go task, the reaction time to the target (RTT), the percentage of correct trials (PCT), and the efficiency score (ES) were measured. Results The findings revealed a significant interaction between group × time for MMSE (F (1, 40) = 20, p < 0.001, h2 = 0.33), and the post-hoc paired-samples t-tests revealed a substantial rise in the mean MMSE in the real group (t = 15.9; p = 0.001; d = 9.3). Additionally, for ES (F (1, 40) = 19, p < 0.001, h2 = 0.32), RTT (F (1, 40) = 17, p < 0.001, h2 = 0.38), and PCT (F (1, 40) = 13, p < 0.001, h2 = 0.31), a significant group time interaction was discovered, and post-hoc paired-samples t-tests revealed a significant improvement in attention performance of the real group for increases in the mean of ES (F (1,40) = 20, p < 0.001, h2 = 0.33), (t = 5.3, p < 0.001,d = 0.034), decreases in the mean of RTT (t = 4.8; p = 0.001; d = –37.4), and increases in the mean of PCT (t = 2.67; p = 0.015; d = 6.3). Conclusions According to the findings of this study, tPBM had a positive effect on older people’s attention and cognitive abilities.
Clinical scoring systems such as the HEART score can predict major adverse cardiovascular events, but they cannot be used to demonstrate the degree and severity of coronary artery disease. We ...investigated the potential of HEART Score in detecting the existence and severity of coronary artery disease based on SYNTAX score. This multi-centric cross-sectional study investigated patients referred to the cardiac emergency departments of three hospitals between January 2018 and January 2020. Data including age, gender, risk factors, comorbidities, 12-lead ECG, blood pressure and echocardiogram were recorded for all the participants. Serum troponin I level was measured on admission and 6 h later. Coronary angiography was done via the femoral or radial route. HEART and SYNTAX scores were calculated for all patients and their association was assessed. 300 patients (65% female) with mean age of 58.42 ± 12.42 years were included. mean HEART Score was 5.76 ± 1.56 (min = 3, max = 9), and mean SYNTAX score was 14.82 ± 11.42 (min = 0, max = 44.5). Pearson correlation coefficient was 0.493 between HEART Score and SYNTAX score which was statistically significant (P < 0.001). We found that HEART Score of more than 6 is 52% sensitive and 74.7% specific to detect extensive coronary artery involvement (SNTAX score ≥ 23). The present study showed that the HEART score has a moderate and positive correlation with the SYNTAX score and HEART score with a cut-off value of 6 is a predictor for SYNTAX score of ≥ 23.
Introduction Isolation and self-quarantine can expose individuals, particularly older people, to cognitive and physical decline. Due to a reduction in their musculoskeletal and neural flexibility, ...older adults are more likely to be affected by quarantine limitations. This study aimed to investigate the effect of self-quarantine on cognitive and balance performance of older women during the COVID-19 outbreak. Material and methods In a convenience sampling method, a total of 75 older adult women were recruited in this ex post facto study. The mini-mental state exam, single leg stance test, and timed up and go test were used to assess cognitive functions, static, and dynamic balance, respectively. Fall risk was measured by the Johns Hopkins assessment tool. Evaluations were performed before and after 7 months of quarantine due to the COVID-19 outbreak (November 2019 – June 2020), in which volunteers were at the lowest level of physical and social interaction. Results No significant difference was observed in the mean static balance performance of the older adult women between the baseline and quarantine phases p = 0.095, t (df) = –1.69. The dynamic balance performance p < 0.001, t (df) = 5.6 and cognitive status (p < 0.001, t = –7.4) decreased and the fall rate increased p < 0.001, t (df) = 7.35 after 7 months of quarantine. Conclusions It seems that self-quarantine can cause a decline in cognitive functions and dynamic balance performance of older women. It implies that the decrease in social interactions and physical activities caused by the limitations of self-quarantine put individuals at greater risk of cognitive impairment and increase their falling rate by impairing dynamic balance.
Group 2 innate lymphoid cells (ILC2) are important in effector functions for eliciting allergic inflammation, parasite defense, epithelial repair, and lipid homeostasis. ILC2 lack rearranged ...Ag-specific receptors, and although many soluble factors such as cytokines and lipid mediators can influence ILC2, direct interaction of these cells with the microenvironment and other cells has been less explored. Natural cytotoxicity receptors are expressed by subsets of group 1 ILC and group 3 ILC and thought to be important for their effector function, but they have not been shown to be expressed by ILC2. Therefore, we sought to investigate the expression and functional properties of the natural cytotoxicity receptor NKp30 on human ILC2. A subset of ex vivo and cultured ILC2 express NKp30 that upon interaction with its cognate activatory ligand B7-H6 induces rapid production of type 2 cytokines. This interaction can be blocked by NKp30 blocking Ab and an inhibitory ligand, galectin-3. Higher expression of B7-H6 was observed in lesional skin biopsies of patients with atopic dermatitis, and incubation of keratinocytes with proinflammatory and type 2 cytokines upregulated B7-H6, leading to increased ILC2 cytokine production. NKp30-B7-H6 interaction is a novel cell contact mechanism that mediates activation of ILC2 and identifies a potential target for the development of novel therapeutics for atopic dermatitis and other atopic diseases.
The important association of erythropoietin (EPO) serum levels and chronic obstructive pulmonary disease (COPD) with anemia has been inadequately studied and remains a controversial issue. We aimed ...to shed light on this matter by comparing EPO levels in anemic and non-anemic COPD patients, along with a review of published literature. This cross-sectional study was conducted on COPD patients referred to the pulmonary clinic of Shahid Faghihi Hospital and Motahari clinic, Shiraz, Iran, for one year. We measured complete blood count, red blood cell indices, serum iron, TIBC and ferritin levels, serum EPO levels, and body mass index. Among 35 patients in this study, 28 males and 7 females were enrolled with a mean age of 54.57 ± 8.07 years. The average Forced expiratory volume in first second (FEV1) was 37.26 ± 7.33% and FEV1/FVC was 0.46 ± 0.12. Mean EPO levels were 30.29 ± 2.066 mU/mL. No statistically significant association was observed among erythropoietin levels and Hb, COPD severity, and age. There was no significant difference in EPO levels between anemic and non-anemic patients. EPO level, against the traditional expectation, didn't increase in COPD patients. EPO production also didn't compensate for the anemia of chronic disease which considers as a common comorbid disorder in these patients.
PDF
