- |||||||||| Preclinical, Journal: Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection. (Pubmed Central) - Feb 27, 2022
When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells.
- |||||||||| Journal: Modulation of Adhesion Molecules Expression by Different Metalloproteases Isolated from Bothrops Snakes. (Pubmed Central) - Feb 23, 2022
Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment.
- |||||||||| Journal, IO biomarker: CD49d marks Th1 and Tfh-like antigen-specific CD4 + T cells during Plasmodium chabaudi infection. (Pubmed Central) - Feb 4, 2022
In adoptive transfer experiments, both CD49d hi and CD49d lo PbT-II cells differentiated into CD49d hi Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49d hi and CD49d lo phenotypes were generally maintained in mice infected with P. chabaudi. These results suggest that CD49d is expressed on Th1-type Plasmodium-specific CD4 + T cells, which are localized in red pulp of the spleen, and can be used as a marker of antigen-specific Th1 CD4 + T cells, rather than that of all pathogen-specific CD4 + T cells.
- |||||||||| Bay11-7082 / InvivoGen
Preclinical, Journal: Heme induces significant neutrophil adhesion in vitro via an NFκB and reactive oxygen species-dependent pathway. (Pubmed Central) - Feb 4, 2022
Notably, heme (50 µM) significantly induced NFκB translocation in neutrophils, and inhibition of NFκB activity with the BAY11-7082 molecule abolished heme-induced cell adhesion to fibronectin and significantly decreased CD11a activity...Thus, our data indicate that heme, at clinically relevant concentrations, is a potent activator of neutrophil adhesion, increasing the ligand affinity of the β2 integrins via a mechanism that may be partially mediated by an NFkB-dependent pathway and the generation of ROS. Given the fundamental role that the adhesion of neutrophils to the vascular wall plays in SCD vaso-occlusion and other vascular inflammatory processes, our findings provide further evidence that cell-free heme is a major therapeutic target in the hemolytic diseases.
- |||||||||| Preclinical, Journal: RNA sequence analysis reveals ITGAL/CD11A as a stromal regulator of murine low-grade glioma growth. (Pubmed Central) - Jan 20, 2022
Given the fundamental role that the adhesion of neutrophils to the vascular wall plays in SCD vaso-occlusion and other vascular inflammatory processes, our findings provide further evidence that cell-free heme is a major therapeutic target in the hemolytic diseases. Collectively, these findings establish ITGAL/CD11A as a critical microglia regulator of LGG biology relevant to future stroma-targeted brain tumor treatment strategies.
- |||||||||| Journal, Epigenetic controller: Histone deacetylase 1 controls CD4 T cell trafficking in autoinflammatory diseases. (Pubmed Central) - Jan 19, 2022
This correlated with reduced expression levels of LFA-1 integrin chains CD11a and CD18 as well as of selectin ligands CD43, CD44 and CD162 on transferred circulating HDAC1-deficient CD4 T cells. Our data reveal that HDAC1 controls T cell-mediated autoimmunity via the regulation of CD4 T cell trafficking into the CNS and intestinal tissues.
- |||||||||| Clinical, Journal: Expression of CD11a, CD11b, CD11c, and CD18 on Neutrophils from Different Clinical Types of Malaria in Malawian Children. (Pubmed Central) - Jan 13, 2022
In areas where Plasmodium falciparum malaria is hyperendemic, such as where this study was conducted, neutrophils have reduced expression of adhesion molecules and activation markers during acute stages of the infection, regardless of the clinical type of malaria. This reduced expression could be due to an individual's past exposure to P. falciparum or other parasite-related factors that manifest during active malaria that still need to be investigated.
- |||||||||| Entyvio (vedolizumab) / Takeda
Identifying CES-1 positive myeloid cells with mass cytometry as a potential therapeutic target for Crohn’s disease (Virtual Poster exhibition) - Dec 29, 2021 - Abstract #ECCOIBD2022ECCO_IBD_822;
PBMCs were collected from CD patients who were receiving Vedolizumab (VDZ) treatment and categorized as responders or non-responders...Conclusion We demonstrated specific CES-1 positive myeloid cells within intestinal biopsies, PBMCs of non-responsive patients, and fistulae samples of CD patients. Targeting CES-1+ with ESM-technology could provide new therapeutic targets for CD.
- |||||||||| Journal, IO biomarker: Impact of CD138 Magnetic Bead-based Positive Selection on Bone Marrow Plasma Cell Surface Markers. (Pubmed Central) - Dec 17, 2021
The change in immunophenotype of the plasma cells on magnetic sorting should be kept in mind when isolating plasma cells using CD138-positive selection for analysis of plasma cells. The technique for characterizing plasma cells should be selected based on the study design to prevent loss of crucial and valuable information.
- |||||||||| cisplatin / Generic mfg., docetaxel / Generic mfg.
Journal: Key immune-related gene ITGB2 as a prognostic signature for acute myeloid leukemia. (Pubmed Central) - Nov 5, 2021
Drug sensitivity test results indicated that the high-risk group was sensitive to cytarabine, axitinib, bosutinib, and docetaxel, but resistant to cisplatin and bortezomib. In the present study, we found that ITGB2 may be able to serve as a biomarker for assessing prognosis and drug sensitivity in AML patients.
- |||||||||| Single-Cell Analysis By Mass Cytometry Reveals CD19 CAR T Cell Spatiotemporal Plasticity in Patients (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4438;
We revealed remarkable diversification within patients CAR T cells and their spatiotemporal relationship to T cells specialization within the human immune system and identified tissue specific CAR T cell expression profiles. Our work provides a potential framework to remodel CAR T cells for enhanced immunotherapy efficacy.
- |||||||||| namodenoson (CF102) - Can / Fite
Adenosine Signaling Perturbs Erythropoiesis and Promotes Myeloid Differentiation (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3591;
Both BAY60-6583 and CI-IB-MECA increased apoptosis and decreased erythroblast maturation and enucleation, while only Cl-IB-MECA led to the upregulation of CD33 and CD11a myeloid markers and promoted the differentiation of a GPA neg myeloid subpopulation...While the activation of A 2B hampers optimal erythropoiesis without impacting the myeloid differentiation. As both ineffective erythropoiesis and increased leucocyte counts are reported in SCD, and given the detrimental role of high adenosine levels in its pathophysiology, further studies are ongoing to address the impact of adenosine signaling on hematopoiesis in this disease.
- |||||||||| Journal: Bacterial species-specific modulatory effects on phenotype and function of camel blood leukocytes. (Pubmed Central) - Oct 30, 2021
The different responsiveness of monocytes and granulocytes toward different bacterial species indicates different host-pathogen interaction mechanisms for the two cell populations. In addition, the phenotypic and functional differences between cells stimulated with E. coli, S. aureus, or S. agalactiae suggests pathogen-species-specific modulating effects of the bacterial pathogens on the camel innate myeloid cells.
- |||||||||| Preclinical, Journal: ICAM-1 and ICAM-2 Are Differentially Expressed and Up-Regulated on Inflamed Pulmonary Epithelium, but Neither ICAM-2 nor LFA-1: ICAM-1 Are Required for Neutrophil Migration Into the Airways In Vivo. (Pubmed Central) - Oct 27, 2021
Although β integrins interacting with ICAM-1 and -2 mediated neutrophil migration across human bronchial epithelium in vitro, neither ICAM-2 nor LFA-1 binding of ICAM-1 mediated murine neutrophil migration into the lung or broncho-alveolar space during LPS-induced inflammation in vivo. Furthermore, TEpM of neutrophils themselves resulted in increased epithelial junctional permeability and reduced barrier function in vitro. This suggests that although β integrins interacting with ICAMs may regulate low levels of neutrophil traffic in healthy lung or early in inflammation when the epithelial barrier is intact; these interactions may be redundant later in inflammation when epithelial junctions are disrupted and no longer limit TEpM.
- |||||||||| Protease Nexin-1, a serpine participating in neutrophil recruitment through CD11a integrin regulation () - Oct 18, 2021 - Abstract #ECTH2021ECTH_38;
This suggests that although β integrins interacting with ICAMs may regulate low levels of neutrophil traffic in healthy lung or early in inflammation when the epithelial barrier is intact; these interactions may be redundant later in inflammation when epithelial junctions are disrupted and no longer limit TEpM. Our results demonstrated that neutrophil PN-1 promotes neutrophil recruitment and activity and could play an important role in the inflammatory reaction.
- |||||||||| [VIRTUAL] Pro-Inflammatory HLA-DRhi Intermediate Monocytes Are Increased in CKD () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_1530;
CCL5 and CX3CL1-dependent chemo-attraction and CX3CL1-dependent endothelial adhesion of monocytes are increased in CKD. The results highlight targetable mechanistic links between intermediate monocytosis, accelerated atherosclerosis and progressive renal injury in CKD.
- |||||||||| Preclinical, Journal: LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils. (Pubmed Central) - Sep 29, 2021
Mechanistically, TLR4/MyD88/PI3Ks regulate the activation of p65, which controls memory-like responses in mouse bone marrow neutrophils (p < 0.05). Our results open a new window for further in vitro studies on memory-like inflammatory responses of short-lived innate immune cells such as neutrophils.
- |||||||||| The neutrophil-specific importance of 2 integrins for the effective defense against invasive pulmonary aspergillosis (A5) - Sep 20, 2021 - Abstract #DGHO2021DGHO_880;
This study demonstrates that β2-integrins are required specifically for antifungal PMN effector functions and contribute to the clearance of A. fumigatus and the establishment of an inflammatory microenvironment in infected lungs as part of the innate immune response. Further studies are needed to clarify the PMN-specific role of β2-integrins in the adaptive immune response with regard to the interaction of PMN with dendritic cells.
- |||||||||| Preclinical, Journal: Glucagon Reduces Neutrophil Migration and Increases Susceptibility to Sepsis in Diabetic Mice. (Pubmed Central) - Sep 19, 2021
Altogether, our results suggest that glucagon may be involved in the reduction of neutrophil migration and increased susceptibility to sepsis in diabetic mice. This work collaborates with better understanding of the increased susceptibility and worsening of sepsis in diabetics, which can contribute to the development of new effective therapeutic strategies for diabetic septic patients.
- |||||||||| Visudyne (verteporfin) / Novartis
Abscopal Effect of Intratumoral Photodynamic Therapy Is Associated with Increased Tumor Directed T Cells (Shoreline Exhibit Hall) - Sep 8, 2021 - Abstract #ACG2021ACG_588;
He was declared as a poor surgical candidate and was started on EUS-guided verteporfin-based PDT...The treatment leads to significantly higher levels of tumor-directed T-cells that are responsive to anti-PD1 directed therapy. These observations suggest the potential of using PDT in combination with immune checkpoint inhibitors in pancreatic cancer.
- |||||||||| Preclinical, Journal: Altered cell surface receptor dynamics and circulatory occurrence of neutrophils in a small animal fracture model. (Pubmed Central) - Aug 18, 2021
Our fundamental new findings of the changes in circulatory neutrophil count and functionality after trauma form an excellent basis for future studies to further elucidate the role of neutrophils as activators and regulators of different post-traumatic processes, potentially resulting in local (e.g., fracture healing disturbances) or systemic (e.g., MODS) complications. This might result in the development of specific therapies to reduce adverse outcomes after trauma.
- |||||||||| Clinical, Review, Journal: Human neutrophil antigens: Nature, clinical significance and detection. (Pubmed Central) - Aug 15, 2021
This review will outline the associated clinical conditions that require HNA investigation and how these are performed in specialized laboratories. Investigations provided are both reactive for patients with a variety of existing or suspected neutropenias and proactive in the testing of blood component donors in order to reduce the potential risk to patients who require transfusion.
- |||||||||| Journal, IO biomarker: Increasing LFA-1 Expression Enhances Immune Synapse Architecture and T Cell Receptor Signaling in Jurkat E6.1 Cells. (Pubmed Central) - Aug 10, 2021
The enhancement in early signaling E6.1 LFA-1 cells did not affect expression of the early activation marker CD69 but led to an increase in IL-2 expression. Our results highlight a new role for LFA-1 in the core architecture of the IS that can be exploited to study the spatiotemporal redistribution of surface receptors on SLBs, thereby extending the potential of E6.1 cells and their derivatives for fine-scale imaging studies.
- |||||||||| Clinical, Journal: Leukocyte populations in peripheral blood of dromedary camels with clinical endometritis. (Pubmed Central) - Aug 7, 2021
Collectively, the results from the current study allowed for identification of associations between endometritis severity grade and larger numbers of inflammatory monocytes. The results also indicate there is no association between endometritis pathogen-species and changes in phenotype or composition of blood leukocytes.
- |||||||||| Review, Journal: β2 Integrin Signaling Cascade in Neutrophils: More Than a Single Function. (Pubmed Central) - Jul 9, 2021
In this review, we focus mainly on inside-out and outside-in signaling of these two β2 integrin members expressed on neutrophils and describe differences between various neutrophil stimuli with respect to integrin activation, integrin ligand binding, and the pertinent differences between mouse and human studies. Last, we discuss how integrin signaling studies could be used to explore the therapeutic potential of targeting β2 integrins and the intracellular signaling cascade in neutrophils in several, among other, inflammatory conditions in which neutrophil activity should be dampened to mitigate disease.
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