- |||||||||| rabeximod (ROB 803) / Cyxone
Preclinical, Journal: NCM 1921, a Mixture of Several Ingredients, Including Fatty Acids and Choline, Attenuates Atopic Dermatitis in 1-Chloro-2,4-Dinitrobenzene-Treated NC/Nga Mice. (Pubmed Central) - Oct 27, 2020
NCM 1921 normalized the total cell number in dorsal skin tissue, the axillary lymph node, and spleen following DNCB exposure and reduced the number of CD23+/B220+ cells in the axillary lymph node and CD3+ cells in dorsal skin tissue...Immunohistofluorescence staining showed that NCM 1921 treatment significantly increased claudin1, filaggrin, and Sirt1 protein expressions in AD skin lesions. These results suggest that NCM 1921 could be a valuable remedy for the treatment of AD.
- |||||||||| rabeximod (ROB 803) / Cyxone, Zyclara (imiquimod) / Mochida, Mylan, Bausch Health, Vesimune (imiquimod intravesical) / UroGen
[VIRTUAL] An Inducible Model of Early Lupus Nephritis (On-Demand) - Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_2271;
This study characterises the IMQ model of LN revealing CD44hi T cell activation and TEM evidence of immune deposits reminiscent of human class II lupus. Treatment for 5 weeks is well tolerated without overt renal failure and creates a model for studying the early pathways involved in immune complex GN and associated therapeutic targets.
- |||||||||| rabeximod (ROB 803) / Cyxone
Preclinical, Journal: A novel monoclonal antibody against human B7-1 protects against chronic graft-vs.-host disease in a murine lupus nephritis model. (Pubmed Central) - Sep 18, 2020
Direct immunofluorescence analysis of the kidneys revealed that immunofluorescence of immune complex deposits was weaker in the 4E5-treated mice and electron microscopy analyses of renal tissues indicated that pathological injury of the kidneys of 4E5-treated mice was decreased compared with that in the model control mice. The results of the present study demonstrated that inhibition of the B7-1/CD28 co-stimulatory signaling pathway with the 4E5 mAb may represent a promising strategy to decelerate the progression of LN that is induced by cGVHD with potential for use in the treatment of other autoimmune diseases.
- |||||||||| rabeximod (ROB 803) / Cyxone
Preclinical, Journal: OMIP-061: 20-Color Flow Cytometry Panel for High-Dimensional Characterization of Murine Antigen-Presenting Cells. (Pubmed Central) - Sep 13, 2020
Reagents were carefully selected and optimized for identification of B cells (B220), neutrophils (Ly6G), monocytes and macrophages (Ly6C, CD169, F4/80), and dendritic cells (XCR1, CD172a, CD11c, I-A/I-E, CD24, CD64, pDCA-1, CD103, CD11b)...Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
- |||||||||| rabeximod (ROB 803) / Cyxone
Preclinical, Journal: Whole transcriptome profiling of germinal center B-lymphocytes using a universal, integrated workflow of FACS cell sorting and TempO-Seq® assay. (Pubmed Central) - Aug 26, 2020
After sequential surface labeling, fixation and permeabilization, ic-staining, and TempO-Seq, GC B-cells (∼2-3% of total cells) were FACS-purified based on B220+CD95+GL7+ staining, then sequencing-ready libraries prepared of 100-cell aliquots/sample...Using ic-staining for the cell cycle progression biomarker Ki67, we found that only 40-45% of PP GC B-cells stained positive, presumably undergoing affinity maturation through somatic hypermutation. We measured differential profiles and these and other data will be presented.
- |||||||||| rabeximod (ROB 803) / Cyxone
Journal: Bone Marrow Plasma Cells Modulate Local Myeloid-Lineage Differentiation via IL-10. (Pubmed Central) - Aug 23, 2020
IL-10+ bone marrow plasma cells showed a B220-/CD19-/MHCII low phenotype suggesting that these cells represent a mature differentiation stage...Moreover, we provide evidence that already under homeostatic conditions in the absence of acute immune reactions, bone marrow plasma cells represent a non-redundant source for IL-10 that modulates local myeloid lineage differentiation. This is particularly relevant in older individuals.
- |||||||||| rabeximod (ROB 803) / Cyxone
Journal, IO Biomarker: Loss of MafA and MafB expression promotes islet inflammation. (Pubmed Central) - Aug 19, 2020
However, clusters of CD4+ T and B220+ B cells were associated primarily with adult MafAMafB, but not MafA islets...Further analysis of T cell marker genes revealed a reduction of T cell receptor signaling gene expression in CD8, but not in CD4+ T cells, which was accompanied with a defect in early T cell receptor signaling in mutant CD8+ T cells. These results suggest that loss of MafA impairs both beta- and T cell function affecting the balance of peripheral immune responses against islet autoantigens, resulting in local inflammation in pancreatic islets.
- |||||||||| rabeximod (ROB 803) / Cyxone
Journal, PD(L)-1 Biomarker, IO Biomarker: IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18. (Pubmed Central) - Aug 18, 2020
The proliferating NK cells highly expressed various activation markers such as B220, CD49b (DX5), lysosome-associated membrane glycoprotein 1 (LAMP-1), DNAX accessory molecule 1, perforin, and granzyme B and showed reduced expression of natural killer cell p46-related protein (NKp46) and IL-18Rα...Some IL-15/IL-18-induced cells strongly expressed PD-1, whereas NK cells induced with IL-15/IL-18 and IL-12 expressed high levels of T cell immunoglobulin mucin-3, LAG-3, and natural killer group 2 A. Furthermore, these cells spontaneously secreted IL-10 and TGF-β following prolonged incubation. Thus, IL-12 regulates expansion of NK cells activated with IL-15/IL-18, influences the population size of highly cytotoxic cells, and induces differentiation to unique cells sharing some phenotypes of ILCs.
- |||||||||| sirolimus / Generic mfg.
Clinical, Observational data, Journal: Cellular Mechanisms of Rejection of Optic and Sciatic Nerve Transplants: An Observational Study. (Pubmed Central) - Aug 9, 2020
Then, we assessed the efficacy of CTLA4 Ig, Rapamycin, and anti-CD3 antibody in suppressing immune cell infiltration of the nerve allografts...Treatment with anti-CD3 antibody reduced immune cell infiltrates in the optic nerve allograft, but exerted no significant effect in the sciatic nerve allograft. These findings establish the feasibility of a preclinical allogenic nerve transplantation model and provide the basis for future testing of directed, high-intensity immunosuppression in these mice.
- |||||||||| rabeximod (ROB 803) / Cyxone
Journal, IO Biomarker: Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease. (Pubmed Central) - Jul 22, 2020
We observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), and increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to the previously described features of an inverted CD4/CD8 ratio, CD4+ T lymphocytopenia, increased B cells, dysgammaglobulinemia, and decreased expression of the natural killer group 2, member D (NKG2D) receptor...Transfection of MAGT1 mRNA enabled us to rescue proteins with defective glycosylation. Together, these data provide new clinical and pathophysiological foundations with important ramifications for the diagnosis and treatment of XMEN disease.
- |||||||||| rabeximod (ROB 803) / Cyxone, PF-573228 / Pfizer
[VIRTUAL] Blocking Focal adhesion kinase (FAK) protects against damage in a novel model of lymphocyte dominant lung injury (Channel 3) - Jul 15, 2020 - Abstract #ERS2020ERS_4574;
Histology and immunofluorescence showed airway thickening, increased mucus production and extensive B220+cell infiltration consistent with a sustained inflammatory response...A FAK inhibitor, PF-573228, was administered at the same time as ova during both the sensitization and challenge phases...In summary, inhibition of FAK preserved lung architecture, prevented vascular leakage and limited leukocyte recruitment. Our data suggest that a chronic adjuvant-free ovalbumin model is useful for examining chronic lung inflammation in mice and that FAK plays a previously unrecognized role in regulating inflammation.
- |||||||||| rabeximod (ROB 803) / Cyxone
Journal: Viral vector and route of administration determine the ILC and DC profiles responsible for downstream vaccine-specific immune outcomes. (Pubmed Central) - Jul 8, 2020
In addition, following i.n. delivery Rhinovirus (RV) and Adenovius type 5 (Ad5) vectors that induced elevated ILC2-derived IL-13, NKp46 ILC1/ILC3-derived-IFN-γ and no IL-17A, predominantly recruited CD11b B220 plasmacytoid DCs (pDC)...Our data also revealed that vector-specific replication status and/or presence or absence of immune evasive genes can significantly alter the ILC and DC activity. Collectively, our findings suggest that understanding the route- and vector-specific ILC and DC profiles at the vaccination site may help tailor/design more efficacious viral vector-based vaccines, according to the pathogen of interest.
- |||||||||| [VIRTUAL] IL-10+ regulatory B cell migration into inflamed skin limits cutaneous inflammation () - Jul 1, 2020 - Abstract #SID2020SID_149;
The decrease accumulation of IL-10+ regulatory B cells was associated with a significant increase in the clinical and histopathological parameters of skin inflammation in both skin inflammation models. Thus, our data show a crucial function of skin-homing IL-10+ regulatory B cells in the suppression of IL-17- and IFN-γ-dominated skin inflammation; supporting the notion that B regulatory cells are critical players in the cutaneous environment during inflammatory skin diseases.
- |||||||||| rabeximod (ROB 803) / Cyxone
Preclinical, Journal: Myocardial maladaptation to pressure overload in CB2 receptor-deficient mice. (Pubmed Central) - Jun 29, 2020
Our study provides mechanistic evidence for the role of the endocannabinoid system in myocardial adaptation to pressure overload in mice. The underlying mechanisms include production of anandamide, adaptation of contractile elements and antioxidative enzymes, and selective modulation of immune cells action and apoptosis in order to prevent the loss of cardiomyocytes.
- |||||||||| rabeximod (ROB 803) / Cyxone
Journal: IL-17A neutralizing antibody regulates monosodium urate crystal-induced gouty inflammation. (Pubmed Central) - Jun 19, 2020
Collectively the results of this study report for the first time, that i.a. injection of MSU crystals stimulates in vivo production of Th17 cells and Th17-related inflammatory cyto-chemokines. In addition, we have demonstrated that the administration of a neutralizing antibody against IL-17 attenuates joint symptoms, swelling and leukocytes infiltration to the inflamed tissue, possibly providing a new strategy for the treatment of gouty inflammation and/or arthritis.
- |||||||||| rabeximod (ROB 803) / Cyxone
[VIRTUAL] Recipient LAG3 Deficiency Results in Antibody-Mediated Rejection of Mouse Renal Allografts (Virtual) - May 29, 2020 - Abstract #ATC2020ATC_1614;
The numbers of B220+CD138+plasma cells were significantly increased in the spleen of LAG3 deficient mice whereas other B cell subsets were not altered... Taken together, these results suggest the predominant role of alloantibody rather than T cells in renal allograft injury and identify LAG3 is a potential therapeutic target for the prevention and treatment of antibody mediated rejection.
- |||||||||| rabeximod (ROB 803) / Cyxone
[VIRTUAL] Agonistic Anti-CD272 Antibody (6B2) Suppressed Donor Specific Antibody Through Inducible Regulatory T Cells (Virtual) - May 29, 2020 - Abstract #ATC2020ATC_1599;
Taken together, these results suggest the predominant role of alloantibody rather than T cells in renal allograft injury and identify LAG3 is a potential therapeutic target for the prevention and treatment of antibody mediated rejection. 6B2 could induce the prolongation of fully MHC-mismatched cardiac allograft through an increase of CD4+CD25+Foxp3+ regulatory T cells and consequently the suppression of DSA.
- |||||||||| rabeximod (ROB 803) / Cyxone, FTY720, fingolimod / Generic mfg.
[VIRTUAL] Marginal Zone B Cells Support Donor-Specific Alloantibody Responses to Heart Allografts (Virtual) - May 29, 2020 - Abstract #ATC2020ATC_1312;
Our results indicate that MZ B cells are required for optimal DSA responses to vascularized heart allografts. While MZ B cells are sufficient to support early IgG DSA production, the defects in DSA are not limited to early stages suggesting that MZ B cells orchestrate subsequent immune responses by FO B cells.
- |||||||||| rabeximod (ROB 803) / Cyxone
Review, Journal, IO Biomarker: The role of BAFF and APRIL in rheumatoid arthritis. (Pubmed Central) - May 27, 2020
Furthermore, overexpressing BAFF augments the number of peripheral B220+ B cells with a normal proliferation rate, high levels of Bcl2, and prolonged survival and hyperactivity. Therefore, in this review article, we studied BAFF and APRIL as important mediators in B-cell and discussed their role in rheumatoid arthritis.
- |||||||||| rabeximod (ROB 803) / Cyxone
Preclinical, Journal: Depletion of CD11c+ dendritic cells in apolipoprotein E deficient mice limits angiotensin II induced abdominal aortic aneurysm formation and growth. (Pubmed Central) - May 25, 2020
Flow cytometry revealed significantly lower numbers of circulating CD44hi CD62Llo effector CD4 T cells, CD44hi CD62Llo effector CD8 T cells and B220+ B cells in CD11c+ cell-depleted mice versus controls...Flow cytometry revealed significantly lower numbers of circulating CD44hi CD62Llo effector CD4 T cells, CD44hi CD62Llo effector CD8 T cells and B220+ B cells in CD11c+ cell-depleted mice versus controls. CD11c+ depletion attenuated SRA matrix degradation indicated by decreased neutrophil elastase activity (p=0.014), lower elastin degradation score (p=0.012) and higher collagen content (p=0.002).
- |||||||||| rabeximod (ROB 803) / Cyxone
[VIRTUAL] IRS2 IS REQUIRED TO EFFICIENT ERYTHROID AND MEGAKARYOCYTIC DIFFERENTIATION IN MURINE MODEL () - May 16, 2020 - Abstract #EHA2020EHA_1211;
Hematopoietic subpopulations were characterized by flow cytometry analysis in PB, bone marrow (BM) and/or spleen: BTM (B lymphocytes [B220], T lymphocytes [CD3ε], myeloid cells [CD11b and Gr1]), erythroid progenitors (CD71 and Ter119) and hematopoietic stem cells (HSC) and progenitors (LSK [Lin-Sca-1+C-Kit+]; long-term HSC [LT-HSC: Lin-Sca+c-Kit+CD150+CD48-]; short-term HSC [ST-HSC: Lin-Sca+c-Kit+CD150+CD48+]; multipotent progenitor [MPP: Lin-Sca+c-Kit+CD150-CD48+]; myeloid progenitor [MP: Lin-Sca-1-cKit+]; megakaryocyte–erythrocyte progenitor [MEP: Lin-Sca-1-cKit+CD34-CD16/32-]; common myeloid progenitor [CMP: Lin-Sca-1-cKit+CD34+CD16/32-] and granulocyte–macrophage progenitors [GMP: Lin-Sca-1-cKit+CD34+CD16/32+]) were evaluated...Conclusion Reduction of mature erythrocytes and platelets in the PB along with the increase in HSC and erythroblasts in BM indicate that depletion of Irs2 results in impairment of erythroid and megakaryocyte differentiation. These results corroborate the findings that Irs2 interacts with important receptors involved in hematopoiesis, including EPOR and MPL.
- |||||||||| rabeximod (ROB 803) / Cyxone
[VIRTUAL] CK2 HAS A KEY ROLE IN HEMATOPOIESIS FROM HSC TO MORE DIFFERENTIATED CELLS. () - May 16, 2020 - Abstract #EHA2020EHA_1208;
Flow cytometry was also used to characterize pre/pro, pro and pre B cells in fetal livers, (Lin, IgM, CD127, B220, CD24, CD25 staining), more mature B/T cells (using CD3, B220, CD19 markers), granulocyte and monocyte/macrophages, (GR1,Mac1, F4/80 markers) both in fetal and adult context...The CK2β heterozygous animals presented an expansion of HSCs and an intermediate phenotype for B cells and granulocytes/monocytes; no substantial changes were detected for T cells Conclusion Our data supports the hypothesis that CK2β plays a fundamental role in hematopoietic cells survival and maturation starting from HSCs and precursors. This could add some new insights for the involvement of CK2 in pathologic context as in the leukemic stem cell biology.
- |||||||||| rabeximod (ROB 803) / Cyxone
[VIRTUAL] EX-VIVO HEMATOPOIETIC STEM CELL EXPANSION SYSTEM AS A PLATFORM FOR GENE EDITING () - May 16, 2020 - Abstract #EHA2020EHA_460;
Conclusion We have succeeded in expanding healthy and diseased CRISPR/Cas9-edited HSCs under defined culture conditions ex vivo and have demonstrated that these modified HSCs contribute to hematopoietic reconstitution after transplantation. Our platform will serve as a tool to further the development of targeted gene therapeutic strategies.
- |||||||||| rabeximod (ROB 803) / Cyxone
[VIRTUAL] Factor VIII Does Not Elicit Danger Signals to Innate Immune Cells in Vivo (Virtual Meeting Room 6) - May 14, 2020 - Abstract #ISTH2020ISTH_816;
Spleens were harvested and expression of activation markers CD40, CD86, and MHC class II on splenic B lymphocytes (B220+), dendritic cells (DCs, CD11c+), and macrophages (CD11b+) were analyzed by flow cytometry... This is the first study to demonstrate that FVIII does not upregulate activation markers shortly after a single infusion or repeated intensive exposure to FVIII in HA mice, suggesting a more complex and temporal mechanism involved in inhibitor formation.
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