bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL30—a novel anti-inflammatory cytokine candidate for preventing and treating inflammatory cytokine-induced liver injury in mice. (117.21)
Authors: Dibra Denada , Cutrera Jeffry , Xia Xueqing , Li Shulin 
Published: January 2023

Abstract
The liver is subjected to the lifetime attacks from chronic viral infection, uptake of the therapeutic drugs, life behavior (alcoholic), and environmental contaminants, results in chronic inflammation and fibrosis. It is urgent to discover effective therapeutic agents for preventing and treating livery injury and the ideal drug will be naturally occurring biological inhibitors. Here, we show that IL30 is a potent anti-inflammatory cytokine that inhibits liver toxicity. IL27, which contains IL30 subunit, does not have such a property. Interestingly, IL30 is induced by pro-inflammatory cytokines such as IFNγ. Administration of IL30 via a gene therapy approach prevents and treats both IL12- and IFNγ-induced liver toxicity. These novel observations shed the light on a novel role of IL30 as a therapeutic cytokine that suppresses pro-inflammatory cytokine-associated liver toxicity.
Phenotypic and functional alterations in peripheral blood monocyte subpopulations following short-term physical training (117.32)
Authors: Rhind Shawn , Shiu Maria , Hamilton Christy , Currie Katherine , Thomas Scott , Goodman Jack , Locke Marius 
Published: January 2023

Abstract
Regular exercise can reduce low-grade systemic inflammation contributing to the prevention of chronic disease. Phenotypic and functional alterations in monocyte (MO) subpopulations are implicated in antiinflammatory mechanisms of physical training. Peripheral blood was sampled from 10 healthy males (24.8±4.3 y) before and after short-term endurance training (6-d cycling 2-h/d, 65% VO2peak). Samples were examined by multicolour immunofluorescence staining and flow cytometry. CD14 and CD16 surface markers characterized 3 distinct MO subsets: classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++); the latter two being potent producers of inflammatory proteins. Coexpression of toll-like receptors (TLR2/4), intracellular cytokines (TNF-α, IL-8, IL-1ra, IL-10), nuclear factor (NF)-κB, and oxidative burst (Rho123) were quantified as changes in fluorescence intensity. Total MO counts dropped after training, with significant reductions in intermediate and nonclassical subsets. TNF-α and IL-8 expression decreased in nonclassical and intermediate MO, respectively, with no change in classical. Conversely, IL-10 and IL-1ra increased in classical and intermediate, but were unchanged in nonclassical MO. TLR2/4 were upregulated on all MO, whereas, NF-κB translocation and oxidative burst were suppressed. Our data indicate short-term training modulates the distribution and functional activity of specific MO subsets, consistent with a net antiinflammatory response.
Differential mucosal expression of IL-34 gene in acute and chronic intestinal inflammation (117.8)
Authors: Das Lopa , Kossak Sarah , Lloyd Benjamin 
Published: January 2023

Abstract
An imbalance of mucosal pro- and anti-inflammatory cytokines is crucial in the pathogenesis of inflammatory bowel disease (IBD). IL-34, a newly discovered cytokine involved in macrophage differentiation, induces the production of macrophage chemoattractant protein (MCP)-1 and eotaxin-2 from primary macrophages. The present ongoing study compared mRNA and protein levels of IL-34, mRNA expression of its cognate receptor colony stimulating factor-1 receptor (CSF-1R) and MCP-1 in intestinal biopsies from controls, Crohn’s disease (CD) and ulcerative colitis (UC) patients. Evaluation of mRNA levels revealed that unlike CD, IL-34 mRNA was 5-fold elevated in UC samples, suggesting that IL-34 could be a potential marker for UC pathogenesis. IL-34 protein levels however, did not mirror mRNA levels suggesting post-transcriptional modification. Interestingly in UC, CSF-1R mRNA varied reciprocally to IL-34, suggesting that like IL-34, CSF-1R could be subjected to post transcriptional modification. Micro RNA database revealed that miR-155 was a predicted candidate to block CSF-1R translation. Low CSF-1R expression correlated with very high levels of miR-155 emphasizing the concept of microRNA mediated regulation. MiR-155 levels in CD were down regulated and varied reciprocally with CSF-1R. MCP-1 was elevated in both IBD patients. Our findings suggest that IL-34 mediated immune regulation is different in UC and CD, which might have important consequences for therapeutic intervention.
NK cell IFNγ response to HLA-G: a role for myeloid DCs? (147.10)
Authors: Le Page Michael , John Elisabeth , Christiansen Frank , Witt Campbell 
Published: January 2023

Abstract
Previous studies report that stimulation of freshly isolated Natural Killer (NK) cells with soluble (but not solid-phase) ligand to KIR2DL4 results in IFNγ production. We have found that stimulation of 13-day cultured, activated, KIR2DL4-expressing NK cells with solid-phase (but not soluble) ligand to KIR2DL4 also results in NK cell IFNγ production. Human Leukocyte Antigen-G (HLA-G) has been reported to be the ligand for KIR2DL4, but controversy persists due to the irreproducibility of interactions between HLA-G (in soluble or solid-phase form) and KIR2DL4. In this study, we took freshly isolated NK cells purified by two methods, stimulated with soluble recombinant HLA-G or control, and measured IFNγ response. We observed an IFNγ response only from RosetteSep purified NK cells, and not from Easysep purified cells. Antibody cocktail analysis predicted that dendritic cells would be removed by the Easysep method but not the RosetteSep method. We confirmed the presence of CD11c+ myeloid dendritic cells (mDCs) in the RosetteSep NK cell purification and showed that removal of mDCs by cell sorting negated the IFNγ response. We further found that addition of mDCs to 13-day cultured, activated, KIR2DL4-expressing NK cells enabled IFNγ production in response to soluble HLA-G. Lastly, we have observed HLA-G tetramers binding to mDCs but not NK cells. We therefore hypothesize that mDCs bind and subsequently present “soluble” HLA-G to NK cells in order to induce an IFNγ response.
Involvement of mFPR2 in dendritic cell maturation and trafficking (147.20)
Authors: Chen Keqiang , Liu Ying , Xiang Yi , Huang Jiaqiang , Le Yingying , Gong Wanghua , Yoshimura Teizo , Tessarollo Lino , Gao Ji-liang , Wang Ji Ming 
Published: January 2023

Abstract
Mouse formylpeptide receptor 2 (mFPR2) is a homologue of the human G-protein coupled chemoattractant receptor FPR2 (FPRL1), which interacts with many pathogen and host-derived agonists. Our previous study revealed reduced allergic airway inflammatory and immune responses in mFPR2 deficient (mFPR2-/-) mice in association with diminished dendritic cell (DC) recruitment into the airway and draining lymph nodes. These defects prompted us to investigate the maturation and function of DCs in mFPR2-/- mice. We found that DC maturation, trafficking and induction of T-cell proliferation are impaired in mFPR2-/- mice. In addition, DCs from mFPR2-/- mice exhibited diminished signaling of p38 MAPK and NF-κB triggered by maturation stimulants. Our observations indicate a non-redundant role for mFPR2 in DC maturation and function in immune responses.
Role of co-stimulatory molecules in macrophage regulation of T cell activation (147.3)
Authors: Riggs James , Bartlett Tom , Silberman Dan , Composto Gabriella , Werda Amy , Cua Jackelyn 
Published: January 2023

Abstract
Murine peritoneal cavity (PerC) T cells from C57BL/6J mice respond poorly in vitro to CD3 ligation due to the high concentration of macrophages (Mϕs) found in this cell source. Mϕs suppressed T cell activation primarily by iNOS catabolism of arginine. Rather than costimulating T cell activation, CD28 ligation increased T cell suppression (“cosuppressed”). IFNγ is necessary for suppression as evidenced by the absence of co-suppression with IFNγRKO PerC Mϕs. To further investigate the co-suppression biology of this system, PerC cells from CD28KO, CD80KO, CD86KO, & CD80/86KO (B7KO) mice were studied. PerC T cells from CD28KO & B7KO mice had the lowest number of IFNγ-secreting cells (IFNγSC) & were the least susceptible to Mϕ-mediated suppression. CD86KO PerC cells included more IFNγSC & their T cells were more suppressed than CD80KO T cells. CD28 ligation costimulated B7KO PerC T cells yet cosuppressed both CD80KO & CD86KO PerC T cells, generating more IFNγSC in the latter. These data, consistent with the higher affinity of CD80 for CD28, suggest that CD80 might represent a biomarker for tumor progression, particularly when considered in conjunction with the density of Mϕs/myeloid-derived suppressor cells.
Responsiveness to IL-2 characterizes a stable Foxp3+ subset in mice (148.16)
Authors: Bautista Jhoanne , Gilfillan Susan , Colonna Marco , Hsieh Chyi-Song 
Published: January 2023

Abstract
It has recently been suggested that lymphopenic conditions result in the loss of Foxp3 expression in CD4+ regulatory T (Treg) cells, thereby switching their function from suppressors to autoimmune effectors. To assess the factors that influence stable Foxp3 expression, we followed the fate of highly purified populations of Foxp3hi cells obtained by serial flow cytometric sorting from Foxp3gfp mice. Consistent with previous reports, we observed that a substantial frequency of Foxp3- cells could be generated from 10^4 Foxp3hi cells after transfer into lymphopenic hosts. This frequency was reduced to approximately 2% in the presence of 10^5 co-injected CD4+ filler cells. However, Foxp3hi cells deficient in IL-2 signaling, or cells expressing intermediate levels of Foxp3 (Foxp3int) were much less stable. In fact, Foxp3int cells that fail to upregulate Foxp3 upon in vitro IL-2 stimulation were the least stable. These data therefore suggest that IL-2 and Foxp3 are part of a positive feedback loop that maintains Treg cell lineage stability. Furthermore, it appears that the minimal level of instability in Foxp3hi Treg cells is unlikely to substantially contribute to spontaneous autoimmunity under clinically relevant lymphopenic states such as bone marrow transplantation.
Myelin-specific B cell receptor transgenic mice reveal critical role for B cell accessory function independent of antibodies in pathogenesis of CNS autoimmune disease (148.2)
Authors: Molnarfi Nicolas , Prod'homme Thomas , Weber Martin , Patarroyo Juan , Linington Christopher , Slavin Anthony , Bernard Claude , Wekerle Hartmut , Shlomchik Mark , Zamvil Scott 
Published: January 2023

Abstract
Human myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE) in a B cell-dependent manner, and is associated with MOG-specific antibodies (Abs). Whether B cells serve as antigen presenting cells (APC) for activation of encephalitogenic MOG-specific T cells in EAE induced by MOG is unknown. To distinguish the role of APC function by MOG-specific B cells from MOG-specific Abs, we created MOG-specific B cell receptor (BCR) transgenic (Tg) mice containing B cells that express membrane MOG-specific Ig only (MOGmIg), but cannot secrete Abs. EAE was compared in MOGmIg mice, MOG-specific BCR knock-in (Th) mice that can secrete all isotypes, in B cell-deficient and wild-type (WT) mice. B cell-deficient mice were resistant, confirming the requirement for B cells in human MOG-induced EAE. MOG induced EAE in MOG BCR knock-in mice, WT mice and MOGmIg Tg mice, indicating that B cells provide an accessory (i.e. APC) function, independent of Ab secretion in MOG-induced EAE. To further evaluate B cell function, mixed bone marrow (bm) chimera mice were created that contained B cells that were selectively MHC II-deficient. Mixed bm chimera mice that contained MHC II+ B cells were susceptible to MOG-induced EAE, whereas mice containing MHC II- B cells were resistant, despite MHC II expression on other APC. Our results conclusively demonstrate that independent of their humoral role, B cells provide a critical cellular function in EAE pathogenesis.
Substance P, a key intermediate in the pathogenes Herpetic Stromal Keratitis (148.23)
Authors: Twardy Brandon , Channappanavar Rudragouda , Suvas Susmit 
Published: January 2023

Abstract
Substance P (SP) is a pro-inflammatory neuropeptide that promotes chronic inflammation. In the current study, we ascertain the effects of blocking SP interaction with its receptor NK1R on the development of HSK lesion severity. Spantide I, a NK1R antagonist, is used for blocking SP-NK1R interaction in C57BL/6 mice after ocular HSV-1 infection. Infected mice were treated with Spantide I, either intra-peritoneally (IP) during pre-clinical (day 0-6) and clinical phases (day 7-15) or subconjuntivally (SC) during the clinical phase of the disease. Mice receiving IP or SC treatments during the clinical phase had a significant reduction in the development of corneal lesions. Corneas excised from these mice had a reduced number of neutrophils yet the number of CD4 T cells remained unchanged when compared to control mice. Additionally, IP administration of Spantide I reduced the frequency of IFNγ producing CD4 T cells in the spleen and cervical lymph nodes of infected mice, whereas SC treatments resulted in a lesser proportion of IFN-γ secreting CD4 T cells in the corneal stroma. Moreover, SC inoculation also resulted in a reduced proportion of IL-2 receptor (CD25) expressing CD4 T cells in the infected corneal tissue when compared to control mice. Taken together, our results show that blocking SP-NK1R interaction during the clinical phase of HSK inhibits the development of severe lesions by reducing CD4 T cell activation and number of neutrophils into the corneal stroma.
The effect of exercise on Th migration within an asthmatic lung. (149.11)
Authors: Dugger Kari , Estell Kim , Schwiebert Lisa 
Published: January 2023

Abstract
Exercise greatly influences the immune system; this includes an exercise-mediated redistribution of T cells in vivo. Increasing evidence demonstrates that Th cells play a central role in the pathogenesis of asthma. We reported previously that repeated bouts of aerobic exercise at a moderate intensity ameliorate asthma-related responses, e.g., airway inflammation and hyperresponsiveness. Studies using OVA-sensitized/challenged mice with luciferase expressing T cells provide a novel method to track T cell trafficking patterns in vivo in real-time. We found a significant reduction in proliferation and presence within the asthmatic lung of exercised mice in comparison with sedentary controls. Further, flow cytometry analysis demonstrated a difference in chemokine receptor profiles on the surface of T cells. The presence of CCR7, which mediates the exit out of lungs, was increased on exercised T cells. In addition, transmigration studies show exercised T cells have a decrease in response to chemokine gradients created by the asthmatic lung that arbitrate entry into the site of inflammation, CCL1 and CCL17. These data demonstrates that aerobic exercise training at a moderate intensity decreases Th cell migration into and increases Th cell exit out of the asthmatic lung; thereby, reducing the subsequent inflammation within the asthmatic lung. Future studies will investigate the underlying mechanism of this exercise-induced shift in homing receptor expression patterns on Th cells.
Regulation of Chemokine Receptor 7 expression by NF-κB in Squamous Cell Carcinoma of the Head and Neck (149.3)
Authors: Mburu Yvonne , Egloff Ann Marie , Wang Lin , Seethala Raja , Walker William , Van Waes Carter , Ferris Robert 
Published: January 2023

Abstract
Aberrant expression of CCR7 has been detected in a number of human malignancies and been linked to pro-survival, invasive and metastatic pathways. In squamous cell carcinoma of the head and neck (SCCHN), we previously described the selective upregulation of CCR7 in metastatic tumors. However, the mechanism(s) of CCR7 expression have not been fully determined. In immune cells, inflammatory cytokines are known to upregulate CCR7 through NF-κB dependent mechanisms. Interestingly, NF-κB has been associated with CCR7 expression and an aggressive SCCHN phenotype. Thus, we hypothesized that NF-κB may be a key mediator of invasive and metastatic disease by promoting CCR7 expression in SCCHN tumors. Immunohistochemical staining of SCCHN tumors showed a strong positive correlation between NF-κB and CCR7 expression. Subsequently, we identified several NF-κB binding sites in the CCR7 promoter and investigated their activity using various assays. Our studies show that each κB motif displayed differential protein binding and transcriptional activation. The induction of NF-κB activity significantly increased CCR7 expression, while blocking NF-κB resulted in a corresponding decrease in CCR7 expression. Our findings support a role for NF-κB in the regulation of CCR7 expression in metastatic SCCHN. The observed NF-κB induction of CCR7 and its subsequent downstream pathways provide clinically important therapeutic targets to control the progression and metastasis of SCCHN tumors.
Expression of chemokine receptor CX3CR1 characterizes effector and effector memory CD8+ T cells after viral infection (150.4)
Authors: Moseman E. , von Andrian Ulrich 
Published: January 2023

Abstract
A number of changes in surface marker expression characterize the differentiation of naïve to effector and memory CD8+ T cells. However, no single surface marker has been reported that durably characterizes effector memory (CD62L- and CCR7-) CD8+ T cells and allows distinction from other T cell subsets, in particular central memory CD8+ T cells (CD62L+ CCR7+). We report here the robust surface expression of chemokine receptor CX3CR1 by effector and memory CD8+ T cells following viral challenge. CX3CR1 expression by CD8+ T cells occurred relatively late after activation, appearing on virus specific T cells 4-5 days after LCMV infection. Expression of CD127 increased on CX3CR1hi cells over time and was markedly enriched during the memory phase. Memory CX3CR1hi CD8+ cells did not express central memory associated LN homing molecules CCR7 or CD62L, and failed to enter LNs, while preferentially localizing to peripheral tissues. Memory CX3CR1hi possessed potent cytolytic function while maintaining a modest proliferative capacity following viral rechallenge. These findings characterize CX3CR1 as a robust and distinctly expressed marker to identify long-lived effector memory CD8+ T cell, which to date could only be approximated as cells that express memory markers, but lack lymph node homing receptors. Expression of CX3CR1 by effector memory CD8+ T cells may provide a potent tool for differentially visualizing their in vivo behavior alongside central memory T cells after rechallenge.
Anandamide inhibits FcϵRI-dependent degranulation through a mechanism involving receptor-operated, but not store-operated calcium entry in mast cells (151.7)
Authors: Cervantes Villagrana Rodolfo , Cruz Silvia , González Espinosa Claudia 
Published: January 2023

Abstract
IgE/Antigen-mediated crosslinking of the high affinity IgE receptor (FcϵRI) in mast cells leads to the release of preformed, granule-stored mediators in a calcium-dependent process known as anaphylactic degranulation. Inhibition of degranulation has been proposed for the control of allergic reactions. Cannabinoid (CB) receptors have been recently found to modulate distinct immune responses. The aim of this work was to analyze the effects of the CB agonist anandamide (AEA) on the anaphylactic degranulation triggered by FcϵRI activation in murine bone marrow-derived mast cells. AEA inhibited FcϵRI-induced degranulation in a concentration-dependent manner. The inhibitory effect of AEA was not observable when degranulation was triggered by A23187+PMA or by thapsigargin (Thap). AEA inhibited maximal intracellular calcium increase in response to IgE/Ag, but intracellular calcium riseafter Thap addition was not changed. Results indicate that CB receptor activation inhibits IgE/Ag-dependent degranulation in mast cells modifying the coupling of FcϵRI with a calcium entry distinct from that dependent on intracellular store depletion
Dimeric galectin-1 alters the plasticity and commitment of Th1 and Th17 cells by promoting IL-10 expression.(152.20)
Authors: Cedeno-Laurent Filiberto , Opperman Matthew , Barthel Steven , Dimitroff Charles 
Published: January 2023

Abstract
Plasticity and commitment of T helper (Th) cell lineages are concepts still under debate. Galectin-1 (Gal-1), a β-galactoside-binding protein, was originally thought to mediate immunoregulation exclusively through its pro-apoptotic effects on activated leukocytes; however, new data suggests that Gal-1 also promotes Th2 skewing, and synthesis of tolerogenic dendritic cells driving differentiation of Type 1 regulatory (Tr1) cells. In this report, using our dimeric Gal-1 hFc, we demonstrate that Th1 and Th17 cells express similar Gal-1-binding glycoprotein repertoires and specifically, CD45, as a predominant binding partner. Furthermore, we show that, at high micromolar concentrations, Gal-1hFc drives caspase-independent apoptosis on Th1 and Th17 cells characterized by nuclear translocation of mitochondrial endonuclease G, but not cytochrome c release. Additionally, at a 10-fold lower concentration, Gal-1hFc incubations during Th1 and Th17 cell priming or after full differentiation caused both pro-inflammatory subsets to synthesize IL-10. In vivo confirmation using murine B16 melanoma cells overexpressing (B16 Gal-1hi) or deficient in Gal-1 (B16 Gal-1KD) showed that mice inoculated with B16 Gal-1hi cells contained higher levels of IL-10+ Th1 and Th17 cells than mice inoculated with B16Gal-1KD cells. This novel property reinforces Gal-1’s role in immune evasion of cancer and highlights its importance as a molecular ‘thermostat’ to help control T cell-mediated inflammation.
E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction (153.1)
Authors: Yang Qi , Esplin Brandt , Borghesi Lisa 
Published: January 2023

Abstract
The immune system is replenished by self-renewing hematopoietic stem cells (HSCs) that produce multipotent progenitors (MPPs) with little renewal capacity. E-proteins, the widely expressed basic helix-loop-helix (bHLH) transcription factors, contribute to HSC and MPP activity but their specific functions remain undefined. Using quantitative in vivo and in vitro approaches, we show that E47 is dispensable for the short-term myeloid differentiation of HSCs but regulates their long-term capabilities. E47 deficient progenitors show competent myeloid production in short-term assays in vitro and in vivo. However, long-term myeloid and lymphoid differentiation is compromised due to a progressive loss of HSC self-renewal that is associated with diminished p21 expression and hyper-proliferation. The activity of E47 is shown to be cell-intrinsic. Moreover, E47 deficient HSCs and MPPs have altered expression of genes associated with cellular energy metabolism, and the size of the MPP pool but not downstream lymphoid precursors in bone marrow or thymus is partially rescued in vivo by anti-oxidant. Together, these observations suggest a role for E47 in the tight control of HSC proliferation and energy metabolism, and demonstrate that E47 is not required for short-term myeloid differentiation.