bluuebunny/crossref_metadata_2025_split huggingface dataset:
C-C Chemokines in Allergen-Induced Late-Phase Cutaneous Responses in Atopic Subjects: Association of Eotaxin with Early 6-Hour Eosinophils, and of Eotaxin-2 and Monocyte Chemoattractant Protein-4 with the Later 24-Hour Tissue Eosinophilia, and Relationship to Basophils and Other C-C Chemokines (Monocyte Chemoattractant Protein-3 and RANTES)
Authors: Ying Sun , Robinson Douglas S. , Meng Qiu , Barata Luis T. , McEuen Alan R. , Buckley Mark G. , Walls Andrew F. , Askenase Philip W. , Kay A. Barry 
Published: January 2023

Abstract
The relationship of expression of the C-C chemokines eotaxin, eotaxin 2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4 to the kinetics of infiltrating eosinophils, basophils, and other inflammatory cells was examined in allergen-induced, late-phase allergic reactions in the skin of human atopic subjects. EG2+ eosinophils peaked at 6 h and correlated significantly with eotaxin mRNA and protein, whereas declining eosinophils at 24 h correlated significantly with eotaxin-2 and MCP-4 mRNA. In contrast, no significant correlations were observed between BB1+ basophil infiltrates, which peaked at 24 h, and expression of eotaxin, eotaxin-2, RANTES, MCP-3, and MCP-4 or elastase+ neutrophils (6-h peak), CD3+ and CD4+ T cells (24 h), and CD68+ macrophages (72 h). Furthermore, 83% of eosinophils, 40% of basophils, and 1% of CD3+ cells expressed the eotaxin receptor CCR3, while eotaxin protein was expressed by 43% of macrophages, 81% of endothelial cells, and 6% of T cells (6%). These data suggest that 1) eotaxin has a role in the early 6-h recruitment of eosinophils, while eotaxin-2 and MCP-4 appear to be involved in later 24-h infiltration of these CCR3+ cells; 2) different mechanisms may guide the early vs late eosinophilia; and 3) other chemokines and receptors may be involved in basophil accumulation of allergic tissue reactions in human skin.
Dendritic cells generated in the presence of PGE2 promote IL-17 production in activated CD4+ T cells (100.10)
Authors: Khayrullina Tanzilya , Ganea Doina 
Published: January 2023

Abstract
Dendritic cells (DCs), the most potent antigen presenting cells, play an essential role both in the induction of the immune response and in maintaining tolerance to self antigens. The DCs phenotype and function depend on various factors, including prostaglandins. PGE2 plays an important role in inflammation and autoimmunity through changes in the proinflammatory cytokine profile. We reported previously that PGE2 induces IL-23 in immature DCs. The proinflammatory cytokine IL-23 is associated with autoimmune disorders such as EAE, RA and IBD, primarily through its effect on the proliferation/survival of Th17 effector cells. The purpose of this study was to determine whether generation of DC in the presence of PGE2 affects their response to inflammatory conditions, particularly in terms of the IL-12p70/IL-23 balance. DC were generated in the presence or absence of PGE2 (DCp and DC, respectively), stimulated with LPS, and characterized in terms of cytokine profile. DCp secreted higher levels of the proinflammatory cytokines IL-6, IL-1b and TNFa. In addition, PGE2 shifted the IL-23/IL-12 balance in favor of IL-23. The changes at protein level reflected changes in transcription, with PGE2 upregulating p19 (the IL-23 specific subunit) and downregulating p35 (the IL-12 specific subunit) expression. In addition, DC generated in the presence of PGE2 preferentially induced IL-17 production in activated CD4+ T cells, and administration of DCp to PLP-immunized SJL/J mice exacerbated EAE.
Grant support: 2RO1 AI0562306 (DG) and Dissertation Fellowship from Rutgers University (TK).
Targeting different isoforms of HMGB1 leads to different beneficial effects in preclinical models of sepsis and inflammatory arthritis (100.6)
Authors: An Ling-Ling , Xu Linda , Barber Arnita Sunhe , Mao Shenlan , Mao Su-Yau , LaRosa Gregory J. , Gao Changshou , McCarthy Michael P. , Wu Herren , Kiener Peter A. , Coyle Anthony J. , Audoly Laurent P. 
Published: January 2023

Abstract
HMGB1 is a multifunctional protein that exerts diverse proinflammatory effects when released into the extracellular milieu. Because several HMGB1 isoforms may be generated depending on the activation state of a cell, these isoforms may play distinct roles in different inflammatory disorders. To examine this, we generated a panel of fully human anti-HMGB1 monoclonal antibodies using a phage display approach. The two most potent mAbs, IA-4 and IA-6, displayed comparable binding affinity to HMGB1 (KD=30 and 39nM) and blockade of HMGB1/RAGE binding (IC50=0.9 and 1.2nM). However, only IA-4 but not IA-6 could detect HMGB1 actively secreted from LPS-treated cells. IA-4 and IA-6 were then tested in rodent models of inflammatory arthritis (rat AIA) and sepsis (mouse CLP). IA-4 reduced paw swelling in the rat AIA model (32% inhibition @ 10mg/kg, p&lt;0.05 vs. isotype control, n=32) while IA-6 had little effect. In contrast, only IA-6 but not IA-4 prolonged survival in the mouse CLP model (@ 8mg/kg , p&lt;0.05 vs. isotype control, n=72). IA-4 and IA-6 displayed similar pharmacokinetics and recognized recombinant rodent HMGB1 with equal affinity. In summary, these results suggest that different isoforms of HMGB1 may have distinct in vivo roles and that HMGB1 mAbs targeting these isoforms may provide tailored therapeutics.
Susceptibility of PIR-B deficient mice to Salmonella infection (101.1)
Authors: Torii Ikuko , Oka Satoshi , Hotomi Muneki , Benjamin William H. , Kearney John F. , Takai Toshiyuki , Briles David E. , Kubagawa Hiromi 
Published: January 2023

Abstract
Paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) isoforms are expressed by many blood cell types including B cells, dendritic cells, monocyte/macrophages, granulocytes, mast cells and megakaryocyte/platelets. To determine the role of PIR in infection, various doses of attenuated S. typhimurium (WB335) were inoculated i.v. into PIR-B−/− or wild-type mice. When given high doses of bacteria (&gt;105 CFU), both types of mice died within 3 – 5 days post-infection. However, when given small doses (103– 104 CFU), all PIR-B−/− mice died within 1 – 3 weeks post-infection, whereas many control mice survived. The bacterial loads in liver, spleen and lung tissues during the 1st week of infection were much higher in PIR-B−/− mice than in control mice. PIR-B−/−, but not control, mice developed sepsis around day 7 post-infection. There were no significant differences in serum levels of cytokines (TNFα, IL1), liver enzymes (ALT, AST, ALK) and BUN or in splenic lymphoid and myeloid subsets between PIR-B−/− and control mice. Ingestion of bacteria by phagocytic cells ex vivo was also the same; however PIR-B−/− phagocytic cells exhibited tighter adherence to plates and released more nitrite than control phagocytic cells. These results suggest that PIR-B plays a role in regulating phagocytic cell responses against bacterial infection.
(Supported by NIH/NIAID grant AI042127)
Regulation of inflammatory disease by the fatty acid binding proteins A-FABP and E-FABP (101.12)
Authors: Reynolds Joseph Michael , Liu Qioahong , Brittingham Katherine C , Stout Robert D , Suttles Jill 
Published: January 2023

Abstract
The fatty acid binding protein (FABP) family is a group of highly homologous intracellular lipid receptors with the ability to bind and transport various hydrophobic compounds within the cell. Adipocyte and epidermal FABPs, A-FABP and E-FABP, respectively, are expressed in macrophages and we have previously reported that A-FABP-deficient macrophages display reduced inflammatory function. Subsequently, we have found that deficiency of E-FABP likewise results in reduced inflammatory potential of macrophages. We hypothesized that FABP function may contribute to the pathogenesis of autoimmune inflammatory diseases. Since a prominent role of macrophages in the pathogenesis of human multiple sclerosis (MS) has been well-documented, we evaluated the role of A- and E-FABPs in the development of experimental autoimmune encephalomyelitis, (EAE), the murine model of human MS. FABP-deficient mice exhibit reduced clinical symptoms of EAE, reduced proinflammatory cytokine expression in CNS tissue, and reduced induction of proinflammatory Th1 and Th17 responses. In addition we demonstrate that dendritic cells express high levels of both A- and E-FABPs, and that antigen presentation by FABP-deficient DC and macrophages does not promote proinflammatory T cell responses. Our studies demonstrate that A- and E-FABP act as positive regulators of inflammatory responses, impacting both innate and adaptive immunity.
Increased nitric oxide production by peripheral blood monocytes and selective elevation of serum IgE in patients with systemic lupus erythematosus (SLE). (101.13)
Authors: Khalifa Dalia , Chimezie Patricia , Ahn Soojin , Finkielstein Anna , Dimitrios George , Lee Susan , Ginzler Ellen , Durkin Helen G , Nowakowski Maja 
Published: January 2023

Abstract
Prospective studies of patients with SLE have reported a prevalence of clinically apparent coronary artery disease (CAD) of up to 20%, a marked increase compared with the estimated CAD prevalence rate of 3.5% among healthy females 20–35 years (AHA 1997 Heart and Stroke Statistical Update). Nitric oxide is an important mediator of inflammation associated with vascular damage. We measured nitric oxide production by cultures of peripheral blood monocytes (N= 26) from patients with SLE and determined serum immunoglobulin concentrations (N=19). Elevated immunoglobulin concentrations were observed in sera from 8 patients (42%), and 4 individuals had a selective increase in IgE (&gt;100 IU/ml), with other immunoglobulin isotypes in the normal range. Nitric oxide (NO) production by adherent monocyte cultures from patients with SLE was determined on day 7 using a modified colorimetric Griess reaction to measure nitrite, the stable NO metabolite. The results showed activation in 31% of the patients, with nitrite concentrations exceeding the baseline of 2.8μM more than threefold, reaching 8.8 μM. The mechanism of this in vivo activation of blood monocytes among some patients with SLE remains to be established. Activated monocyte-derived nitric oxide may contribute to the development of atherosclerosis and cardiovascular complications seen in many patients with SLE.
Modulation of apoptosis and the production of reactive oxygen species in human neutrophils with epigallocatechin-3-gallate (EGCG) (101.6)
Authors: Babcock George F , Osterburg Andrew R , Schwemberger Sandy , Hyon Suong-Hyu , Koizumi Takeo 
Published: January 2023

Abstract
Our laboratory has demonstrated that following thermal injury, neutrophils (PMNs) display altered immune responsiveness. Decreased apoptosis was associated with the expression of Heat Shock Protein 72 (HSP72), while increased apoptosis is associated with the production of reactive oxygen species. EGCG is an anti-oxidant found in green tea which possesses immunomodulatory properties. In this study, we investigated the effects of EGCG on PMN apoptosis and the production of reaction oxygen species. Human PMNs (HSP 72 + or −) were treated with tumor necrosis factor (TNF[alpha]) or phorbol myristate acetate (PMA), with or without EGCG. PMNs were analyzed for apoptosis, the production of superoxide anion (O2−), and hydrogen peroxide (H2O2). PMNs treated with EGCG had a significant reduction in the percentage of cells undergoing apoptosis with either agonist (by 78 and 53%, respectively). While PMNs expressing HSP72 had decreased apoptosis compared to controls, treatment with EGCG further decreased the percentage of HSP 72+ PMNs undergoing apoptosis. Treatment with EGCG significantly reduced the production of H2O2 and O2− by PMNs treated with TNF[alpha]or PMA. The data suggests that EGCG significantly reduces apoptosis, H2O2 and O2− in activated PMNs. Due to its low toxicity, ECGC may be an ideal agent to modulate the inflammatory response associated with burn injury.
Supported in part by a grant from Shriners of North America
Recipient Conditioning with Mesenchymal Stem Cells and Interleukin-10 Prolonged Cardiac Allograft Survival (102.1)
Authors: Salgar Shashikumar , Li S , Hernandez M , Wei Y , Mateu D , Vazquez-Padron R , Mathew J , Pham S 
Published: January 2023

Abstract
Mesenchymal Stem Cells (MSC) and viral interleukin-10 (vIL-10) have immunosuppressive properties. In this study, we tested their ability to prevent cardiac allograft rejection. Bone marrow derived MSC from Lewis rat were expanded ex vivo and transduced with rvIL-10-retrovirus. Autologous MSC or vIL-10 transduced MSC were injected (~25 x 106; i.v.) into irradiated (4 Gy) rat (RT1.Al). Six weeks later heterotopic heart (RT1.An) transplantation (Tx) was performed. MSC therapy prolonged (P&lt;0.05) cardiac allograft survival (14±1 days; n= 4) compared to untreated controls (7±1 days; n=4). Also, vIL-10-MSC treatment prolonged (P&lt;0.01) graft survival (38±1 days; n=6) compared to empty vector treated group (15±1 days; n=4). In vIL-10-MSC preconditioned animals that received donor bone marrow after heart Tx, graft survival was 22±2 days (n=8). Intragraft expression of co-stimulatory molecule (CD80) and cytokines (IL-2, IFN-γ) as determined by RT-PCR was lower (P&lt;0.03) in vIL-10-MSC treated grafts compared to untreated control grafts. Ex vivo expanded MSC were CD34−, CD45+(5 %), CD29+(90%), CD80 (0%), CD 86 (8%), CD90+(93%), MHC Class I+(23–57%), and MHC Class II- as determined by FACS. Both vIL-10 and empty vector engineered MSC expressed CD29 (&gt;95%) but not other molecules. The vIL-10-MSC produced ~ 6 ng/ml of vIL-10 ex vivo. vIL-10-MSC addition in MLR cultures inhibited lymphoproliferative response (P&lt;0.05). TGF-β expression in stimulated (TNF-α or IL1-β) and unstimulated MSC was 46 – 65% of β-actin. IL-2, IL-4, IL-10, IFN-γ, and TNF-α expression was negligible in MSC (0–7% of β-actin). VEGF and HGF mRNA expression in MSC was 58% and 5% of β-actin, respectively. TgGFP+ MSC were demonstrable in various tissues for &gt;28 days. Both MSC and vIL-10 conditioning to promote allograft survival seems promising.
DISPLAY OF A NOVEL FORM OF FasL PROTEIN ON ALLOGENEIC ISLETS RESULTS IN PROLONGED GRAFT SURVIVAL (102.13)
Authors: Shirwan Haval , Zhao Hong , Lacelle Chantale , Askenasy Nadir , Yolcu Esma S. 
Published: January 2023

Abstract
Manipulation of donor organs, rather than the recipients, for tolerance induction represents an exciting approach. We have recently developed a novel approach designated as ProtEx™ that allows for the generation of chimeric immunological ligands with core streptavidin (SA) and their display on the biotinylated cell surfaces in a rapid and efficient manner. Chimeric proteins have potent immunological activities, possibly due to their ability to form tetramers and higher structures. We generated a chimeric form of FasL molecule (SA-FasL) with potent apoptotic activity and previously demonstrated that this protein can be displayed on the surface of donor splenocytes in a rapid and efficient manner, and such cells when co-transplanted with islets prevented their rejection in allogeneic hosts. We herein tested if islets can directly be engineered to display SA-FasL on their surface and if such islets become refractive to rejection in allogeneic hosts. BALB/c islets were biotinylated, decorated with SA-FasL, and transplanted into syngeneic or allogeneic C57BL/6 hosts with STZ-induced diabetes. SA-FasL-decorated islets had no observed toxicity and normalized blood glucose levels in 100% of syngeneic hosts. Transplantation of SA-FasL-decorated BALB/c islets into C57BL/6 resulted in prolonged graft survival with &gt;20% of grafts surviving indefinetly. All the islets decorated with the control SA protein were rejected in a normal tempo. Engineering pancreatic islets for the display of SA-FasL in a rapid and efficient manner represents a practical and safe alternative to gene therapy for immunomodulation. NIH (R21 DK61333, R01 AI47864, R21 AI057903, R21 HL080108), JDRF (1-2001-328), and ADA (1-05-JF-56.
A Soluble Factor from Mesenchymal Stem Cells Suppress T cell Proliferation by Induction of IL-10 Production from T cells (102.16)
Authors: Yang Seung-Ha , Yun Il-Hee , Park Chung-Gyu 
Published: January 2023

Abstract
Mesenchymal stem cells (MSCs) have immune modulation effect on T cells. The underlying mechanism is not fully understood. In this study, we investigated the mechanism of immune modulation effect of MSCs on T cell proliferation and its effector function. MSCs from BALB/c and C57BL/6 were identified by surface marker (CD106+, CD45−, CD31−, CD34−, CD11c−, and CD14−) and their differentiation capacity into adipocyte and osteoblast. MSCs from BALB/c expressed neither MHC class I nor II molecules whereas those from C57BL/6 expressed only MHC class I molecule. The co-culture of irradiated MSCs in mixed lymphocyte reactions (MLRs) PMA & ionomycin stimulated T cell resulted in the suppression of T cell proliferation in a dose-dependent manner. In addition, the same suppressive effect was observed on priorly activated T cells. The transwell assay, where T cells were separated from MSCs, showed comparable reduction of T cell proliferation suggesting the role of soluble factors from MSCs on the suppressive effect. The inhibition of T cell proliferation by the addition of MSCs culture supernatant in MLRs confirmed a soluble factor as a T-cell-inhibitory effector mechanism ELISPOT assay demonstrated the addition of MSCs supernatant in MLR markedly increased IL-10(+) cells. Furthermore, T cell proliferation was partially recovered by IL-10R neutralizing antibody. Taken together, these results suggest that IL-10 from activated T cells in the presence of MSCs culture supernatant would be one of the mediators of T cell suppression by MSCs.
This study was supported by a grant of the Korea Health 21 R & D Project, Ministry of Health & Welfare, Republic of Korea. (Project No. : A040004)
Male microchimerism in peripheral blood of women awaiting kidney transplantation correlates positively with HLA allo-immunization (102.19)
Authors: Albano Laetitia , Meynet Ophélie , Cassuto Elisabeth , Bernard Alain , Bernard Ghislaine 
Published: January 2023

Abstract
Microchimerism is the persistence of a small population of donor or fœtal cells, in graft recipients or in mothers. It appears after transfusion, pregnancy, transplantation and has been implicated in graft rejection, tolerance and auto-immunity. Anti-HLA Ab can appear under identical circumstances. Why and how such Ab persist for decades is only partially understood. We questioned if male microchimerism in the peripheral blood of women could be one of the mechanisms allowing the maintenance of anti-HLA Ab production. We evaluated 46 women, waiting for a first kidney graft, for the presence or absence of anti-HLA Ab using an ELISA. A Panel Reactive Ab was determined using Luminex® technology. Y chromosomal DNA was identified by nested PCR using specific primers of the SRY region. All patients were pregnant and/or transfused. In the Ab+ group (n=24), all women were sensitized and in the Ab− group (n=22), all women were unsensitized. Thirty-nine percent of all women (18/46) carried a male microchimerism: 54% in the Ab+ group (13/24) vs. 22% in the Ab− group (5/22) with pχ2= 0.029. We found a significant frequency of male microchimerism in the peripheral blood of women with kidney disease, which positively correlated with the presence of anti-HLA Ab.
MyD88 is required for the Differentiation of Recipient Monocytes into Dendritic Cells and Macrophages in Orthotopic Lung Grafts (102.2)
Authors: Gelman Andrew E , Kreisel Daniel 
Published: January 2023

Abstract
In lung grafts ischemia-reperfusion (I/R) signals rapidly induce the recruitment and differentiation of host monocytes into macrophages and dendritic cells. The nature of these I/R signals are antigen-independent but have been hypothesized to initiate Toll-like receptor (TLR)-mediated signaling pathways that are thought to potentiate alloimmune responses. We asked if MyD88, an adaptor molecule critical for most TLR-mediated inflammatory responses, regulated recipient monocyte differentiation in a mouse model of orthotopic lung transplantation. Orthotopic left lung transplants were performed in the following syngeneic combinations: CD45.1+ B6 → CD45.2+ MyD88−/− and CD45.1+B6 → CD45.2+ B6 (WT). 24 hrs later recipient-derived dendritic cell (DCs: CD45.2+ CD11c+CD11b+IAblo–hi) and macrophage (Macs: CD45.2+ CD11c−CD11b+ IAblo) numbers were assessed in bronchial lavage (BAL) by FACS analysis. Compared to the BAL of WT recipients MyD88−/− recipients had lower mean numbers of Macs (535/ml vs. 1419/ml) and DC’s (651/ml vs. 1763/ml) of recipient origin. Moreover, airway DC’s of lung grafts in MyD88−/− recipients expressed lower levels of IAb, CD40 and CD86 than did their WT counterparts. We also analyzed monocyte differentiation in allogeneic lung recipients by comparing the fate of adoptively transferred CD45.2+CD11b+IAb−Ly6ChiGr1− bone marrow monocyte precursors (MPs) from either MyD88−/− or WT mice in CD45.1+B6 mice that received Balb/c lung grafts. As in the syngeneic graft combinations, adoptively transferred MyD88−/− MPs were similarly defective at differentiation into DCs and macrophages in allografts. In conclusion the data demonstrates that MyD88 regulates recipient monocyte differentiation and suggests a mechanism by which TLR signaling pathways control adaptive responses in lung allografts.
Pre-sensitized B-cells prevent anti-CD154 mediated cardiac allograft tolerance (102.21)
Authors: Troutman Audrea Melody , Ma Lianli , Ding Jinwen , Shen Jikun , Chong Anita 
Published: January 2023

Abstract
Memory T-cells have been identified to be a significant cause of costimulatory resistant rejection; however, the role of pre-sensitized B cells has yet to be elucidated. We have developed a heart transplant model that specifically generates allospecific memory B-cells without generating allospecific memory T-cells. Pre-sensitized 3.83 B-cells with dual-specificity for H-2Kk and H-2Kb were generated in 3.83 BCR (BALB/c background) knock-in mice that received C3H (H-2Kk) hearts. To test whether pre-sensitized 3.83 B-cells can prevent tolerance induction by α-CD154 treatment, C3H-primed 3.83 recipients (30–90d post-C3H heart transplant) received a second heart and treatment with α-CD154. Second B/6 hearts (H-2Kb), which can be recognized by the pre-sensitized 3-83 B-cells, were acutely rejected within 10–13 days despite α-CD154 therapy. To confirm the importance of the pre-sensitized B cells, we transferred only B-cells or T-cells from C3H-presensitized 3.83 mice into naïve BALB/c recipients treated with α-CD154. Only transferred B-cells, but not T-cells, abrogated the tolerogenic effects of α-CD154. Histological examination of the rejected grafts from pre-sensitized 3-83 recipients treated with α-CD154 revealed significant numbers of infiltrating T cells. Also, B/6-specific IFNγ-producing T cells were detected in the pre-sensitized 3.83 recipients treated with α-CD154, but not in similarly treated naïve 3-83 recipients. We conclude that pre-sensitized B-cells are sufficient to prevent tolerance induction by permitting the CD40-CD40L independent activation of alloreactive T cells.
Funding source: NIH Immunology Training Grant.