- |||||||||| Journal: Impact of Psychological Stressors on Natural Killer Cell Function: A Comprehensive Analysis based on Stressor Type, Duration, Intensity, and Species. (Pubmed Central) - Nov 17, 2024
Although the exact mechanisms of NK cell dysfunction under stress remain unclear, potential causes include reduced release of secretory lysosomes with perforin or granzyme, impaired NK cell synapse formation, decreased expression of synapse-related molecules like CD2 or LFA-1 (CD11a), altered activating receptor expression, and dysregulated signaling pathways, such as decreased Erk1/2 phosphorylation and NFkB signaling. These mechanisms are not mutually exclusive, and future research is needed to clarify these pathways and develop therapeutic interventions for stress-induced immune dysregulation.
- |||||||||| International Clinical Consensus on Leukocyte Adhesion Deficiency-I: A Modified Delphi Analysis (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4620;
Conclusions The diagnostic and severity classification framework developed by the Delphi panel will aid clinicians in the diagnosis, classification and treatment of patients with LAD-I. Recommendations support best clinical practice and will lead to improved clinical outcomes among patients with LAD-I.
- |||||||||| HUMAN INHERITED ITGAL (CD11A) DEFICIENCY IMPAIRS CUTANEOUS T-CELL IMMUNITY TO COMMENSAL PAPILLOMAVIRUSES (Auditorium) - Oct 19, 2024 - Abstract #ESID2024ESID_584;
However, loss of LFA-1 preferentially disrupts the skin homing of memory T cells, leading to the accumulation of skin-tropic T cells in the blood and a marked reduction in their number within the skin. Conclusions Human LFA-1 is essential for T-cell-mediated skin immunosurveillance against commensal HPVs, but it is largely redundant for protective immunity against other microbes.
- |||||||||| Review, Journal: The Application of Mesenchymal Stem Cells in Different Cardiovascular Disorders: Ways of Administration, and the Effectors. (Pubmed Central) - Jul 18, 2024
The protective effects of MSCs and their secretomes on the heart are generally attributed to their differentiation into cardiomyocytes and endothelial cells, their immunomodulatory properties, paracrine effects, increasing blood vessel density, cardiac remodeling, and ejection fraction and decreasing apoptosis, the size of the wound, end-diastolic volume, end-systolic volume, ventricular myo-mass, fibrosis, matrix metalloproteins, and oxidative stress. The present review aims to assist researchers and physicians in selecting the appropriate cell type, secretomes, and technique to increase the chance of success in designing therapeutic strategies against cardiovascular diseases.
- |||||||||| Journal: IRG1/ACOD1 Promotes Neutrophil Reverse Migration and Alleviates Local Inflammation. (Pubmed Central) - May 7, 2024
These findings suggest that the binding of ICAM-1 and shed CD11a serves as a retaining force to hold PMNs in the site of inflammation, and ACOD1-decreased PMN surface expression of ICAM-1 weakens the retaining force, so promoting PMNs to leave the inflammatory site. These results indicate a regulatory role of IRG1 in PMN rM and subsequent contributions to inflammation resolution.
- |||||||||| Journal, IO biomarker: Flow cytometric immunophenotypic differentiation patterns of bone marrow eosinophilopoiesis. (Pubmed Central) - Apr 26, 2024
A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.
- |||||||||| Identification of anti-human and mouse mAb cross-reactive to agriculture and wildlife species (Exhibit Hall F1; Poster Board Number: B1035) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1336;
Research to further validate specificity and cross-reactivity of these mAbs with indicated species is ongoing. Identification of commercially-available, fluorescently-labeled mAbs cross-reactive to livestock and wildlife immune cells will enhance relevant research programs across the globe.
- |||||||||| Journal: Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells. (Pubmed Central) - Feb 27, 2024
Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the 'outside-in' signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.
- |||||||||| Journal: Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110. (Pubmed Central) - Feb 10, 2024
We found that the administration of synaptamide increased the expression of its receptor GPR110 in both total kidney tissue and renal CD11b/c+ cells that was associated with the reduced production of pro-inflammatory interleukins in these cells. Thus, we demonstrated that synaptamide therapy mitigates the inflammatory response in kidney tissue during ischemic AKI, which can be achieved through GPR110 signaling in neutrophils and a reduction in these cells' pro-inflammatory interleukin production.
- |||||||||| Review, Journal: Integrins in Health and Disease-Suitable Targets for Treatment? (Pubmed Central) - Feb 9, 2024
However, whereas both agonistic and antagonistic agents yielded beneficial effects in animal models, the success of clinical trials was limited in most cases and was associated with unwanted side effects. This unfavorable outcome is most probably related to the systemic effects of the used compounds on all leukocytes, thereby emphasizing the need to develop formulations that target distinct types of leukocytes to modulate ?2 integrin activity for therapeutic applications.
- |||||||||| Global Proteomics Identifies CDK11A/B As Integral to Myeloma Proliferation and High-Risk Disease (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2361;
Kaplan-Meier estimates of OS PEP60 and OS GEP70 in low-risk myeloma and high-risk myeloma showed increased inferior survival for PEP60 OS (P<0.001; HR = 4.49) compared to GEP70 OS (P<0.001; HR = 3.64). Kaplan-Meier estimates of OS for PEP60high/GEP70high (black), PEP60high/GEP70low (red), PEP60low/GEP70high (brown), and PEP60low/GEP70low (blue) showed significant inferior survival for the PEP60high/GEP70high group (P<0.001, HR = 9.07) compared to PEP60high/GEP70low (P<0.001, HR = 3.70) and PEP60low/GEP70high (P<0.001, HR = 3.03), demonstrating that PEP60 and GEP70 capture separate high-risk patients when only one is high ( Fig 1 ).
- |||||||||| Journal, PD(L)-1 Biomarker, IO biomarker: OMIP-099: 31-color spectral flow cytometry panel to investigate the steady-state phenotype of human T cells. (Pubmed Central) - Oct 10, 2023
This panel also includes markers for the identification of differentiation status (CD27, CD28), activation/antigen experience status (CD11a, CD49d, CD38, HLA-DR, CD56, and CD39), co-inhibitory marker expression (PD-1, TIM-3), and CD4 T helper subsets (CXCR3, CXCR5, CCR4, CCR6, Foxp3, CD25, and CD127). This optimized panel provides a broad assessment of the steady-state phenotype of human T cells.
- |||||||||| Journal: CD11a regulates hematopoietic stem and progenitor cells. (Pubmed Central) - Oct 6, 2023
Rather we found that the production of IL-27, a major cytokine that drives HSPC proliferation, was significantly upregulated both in vivo and in vitro. This adds a novel role of CD11a biology.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Unique T-cell Sub-Population Shifts after SBPT and Nivolumab in Platinum Refractory HNC: Biomarker Correlates from ROR1771 (Hall B2; In Person Only) - Aug 22, 2023 - Abstract #ASTRO2023ASTRO_2097; Biomarker analysis of peripheral blood samples demonstrated significant shifts in T-cell subpopulations and underlying gene expression to nivolumab and then to SBPT administration. SBPT to a target lesion changed TCR clonotypes within the peripheral blood beyond those seen with nivolumab administration, with fading of these TCR clonotypes coinciding with recurrence.
- |||||||||| Imaging Intravascular Macrophages Using Micro-Sized Superparamagnetic Decoys (126A) - Aug 12, 2023 - Abstract #AHA2023AHA_403;
Intravenous injection of superparamagnetic decoys in the micrometer size range allows to image intravascular macrophages. This new method allows to study the pathophysiological roles of intravascular macrophages in experimental models and could be easily translated to humans.
- |||||||||| Biomarker, Journal: Analysis of Novel Immunological Biomarkers Related to Rheumatoid Arthritis Disease Severity. (Pubmed Central) - Aug 12, 2023
Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO (p < 0.0001) and CD45RA (p < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3CD4 lymphocyte percentage (p < 0.0424) and CD45RA (p < 0.0424), CD62L (p < 0.0284), and CD11a (p < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.
- |||||||||| Journal: Clinical and immunological characteristics of 69 leukocyte adhesion deficiency-I patients. (Pubmed Central) - Jul 30, 2023
Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.
- |||||||||| Journal: Decrypting Integrins by Mixed-Solvent Molecular Dynamics Simulations. (Pubmed Central) - Jun 13, 2023
We show that these pockets are putatively accessible to small-molecule modulators. The findings reported here may provide opportunities for the design of novel allosteric integrin inhibitors lacking the unwanted agonism observed with earlier as well as current integrin-targeting drugs.
- |||||||||| MONOCYTE MIGRATION AND ACTIVATION IN ANCA-ASSOCIATED GLOMERULONEPHRITIS (Focussed Oral Room 9) - May 4, 2023 - Abstract #ERAEDTA2023ERA_EDTA_1755;
Our findings on migration are surprising in the light of theorized enhanced monocyte extravasation towards diseased AGN kidneys. Therefore, it could be speculated that after a longer period of time, a subset of the adherent monocytes would ultimately migrate and differentiate into kidney macrophages.
- |||||||||| Xiidra (lifitegrast) / Novartis
Journal: Allosteric targeting resolves limitations of earlier LFA-1 directed modalities. (Pubmed Central) - Apr 25, 2023 This profile differentiates the new generation of allosteric LFA-1 inhibitors from previous ligand mimetic-based LFA-1 inhibitors and anti-LFA-1 antibodies, and is projected to support novel immune regulatory regimens selectively targeting the integrin LFA-1. The rigorous computational and experimental assessment schedule described here is designed to be adaptable to the preclinical discovery and development of novel allosterically acting compounds targeting integrins other than LFA-1, providing an exemplary approach for the early characterisation of next generation integrin inhibitors.
- |||||||||| Glucocorticoids redirect naive T cells to the bone marrow in malnourished mice (P779) (Exhibit Hall; Poster Board No. P779) - Apr 11, 2023 - Abstract #IMMUNOLOGY2023IMMUNOLOGY_1684;
Indeed, similarly low percentages of glucocorticoid receptor deficient T cells were observed in the bone marrow of malnourished and control mice, indicating that T cell expression of the glucocorticoid receptor is required for T cell migration to the bone marrow. Overall, we have determined that malnutrition modifies both the bone marrow and na
- |||||||||| Impact of Surgery on Cytotoxic Activity of Patient-driven CD8 T cell (S405) - Mar 30, 2023 - Abstract #AUA2023AUA_1270;
Higher levels of CD11a, CX3CR1 and GZMB CD8 T cells as well as lower PD-L1 serum levels after surgery were associated with higher cytotoxic activity of patient-derived tumor-reactive effector CD8 T cells. SOURCE OF
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