bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the cross reactive T cell repertoire in the context of heterosubtypic influenza A virus infection
Authors: Gaevert Jessica A , Duan Susu , Thomas Paul Glyndwr 
Published: January 2023

Abstract
Influenza A viruses (IAVs) are a major respiratory pathogen with the capacity to rapidly mutate and escape an individual’s existing immunity to a specific strain generated by vaccination or naturally acquired infection. CD8 T cells however, target conserved proteins that could be shared across multiple subtypes. Heterosubtypic immunity to IAVs, where memory T cells generated to a previous IAV are reactivated during re-challenge with an antigenically distinct virus, may be important in generating an effective immune response to different and/or novel strains of IAV. Specifically, cross reactive T cells, where a T cell receptor (TCR) can recognize more than one epitope displayed on an MHC-I molecule, could facilitate rapid recognition of conserved or nominally divergent epitopes, may have the potential to alter the TCR repertoire over the course of heterosubtypic infections, and might be selected for by the immune system. Utilizing 8 variant influenza viruses for priming and secondary challenge, our preliminary data has shown that cross reactive TCRs seen in primary infection with one IAV can mount a robust and effective memory response to a different IAV, even if the epitope has slightly mutated. However, selection for cross reactive receptors may create a narrowed repertoire consisting of a few clonotypes over the course of many repeated heterosubtypic IAV infections, covering a narrow range of antigenic space representing the mutant epitopes encountered. Paradoxically, this selection for cross-reactivity may provide a substantial escape opportunity with future antigenic variations. Ongoing work focuses on how repeated IAV challenges shape and are shaped by these selected cross-reactive T cell pools.
Non-canonical functions of adaptive natural killer cells
Authors: Gyurova Ivayla E , Win Hannah Than , Waggoner Stephen N 
Published: January 2023

Abstract
Natural killer (NK) cells are critical for the control of cytomegalovirus (CMV) infections in both mice and humans. Subsets of phenotypically and functionally distinct adaptive NK cells accumulate after CMV infection and potentially represent desirable new targets for a preventive CMV vaccine owing to their putatively greater antiviral functionality. However, our lab and others have described a series of non-canonical functions of NK cells that prevent harmful disease outcomes by modulating the responses of other leukocytes. In fact, we now demonstrate that bulk human blood NK cells can suppress CMV-specific T cell responses during in vitro culture. We reason that amplification of these non-canonical functions within an expanded subset of virus-induced adaptive NK cells would be beneficial to health in the context of virus persistence. In order to compare the canonical antiviral and non-canonical immunoregulatory functions of conventional and adaptive NK cells, we first sought to determine if it was possible to expand these subsets using K562 feeder cells with membrane bound IL-21. Similar to our recent longitudinal clinical profiling of adaptive NK cells (Gyurova et al. 2019), we observed variable increase or decrease in the baseline frequencies of adaptive (i.e. FcRγneg) NK cells following ex vivo expansion of cells from disparate healthy donors. Ex vivo expanded NK subsets demonstrated a reduced capacity to kill K562 cells. These results establish a method for obtaining sufficient quantities of adaptive and conventional NK cells for functional evaluation of antiviral and regulatory activity.
SATB1 as a novel therapeutic target for methyltransferase inhibitors against Cutaneous T Cell Lymphoma
Authors: Harro Carly , Perez-Sanz Jairo , Costich Tara Lee , Payne Kyle K , Galindo Carmen Maria Anadon , Gonzalez Ricardo A Chaurio , Biswas Subir , Mandal Gunjan , Rigolizzo Kristen E , Mine Jessica A , Showe Louise C , Liu Kebin , Rodriguez Paulo C , Pinilla-Ibarz Javier Lee , Sokol Lubomir , Conejo-Garcia Jose R 
Published: January 2023

Abstract
Cutaneous T cell lymphoma (CTCL) is a clinically unmet need. Using conditional knockout mice, we found that ablation of the genomic organizer Special AT rich sequence binding protein 1 (Satb1) induces a progressively fatal lymphoma characterized by mature, skin homing, Notch activated CD4 and CD8 T cells. Mechanistically, Satb1 restrains Stat5 phosphorylation and the expression of skin homing chemokine receptors in mature T cells. Notably, SUV39H1 and 2 methyltransferase dependent epigenetic repression of SATB1 is universally found in human Sezary Syndrome, but not other peripheral T cell malignancies. Accordingly, H3K27 and H3K9 trimethylation occlude the SATB1 promoter in Sezary cells. Inhibition of SUV39H1 and 2 methyltransferases with novel drugs, unlike EZH2 inhibition, restores SATB1 expression, selectively abrogating the growth of primary Sezary cells more effectively than Romidepsin. Therefore, SATB1 acts as a tumor suppressor in mature T cells upon NOTCH1 deregulation, and inhibition of methyltransferases that silence SATB1 could address an unmet need for patients with mycosis fungoides and Sezary syndrome.
S. aureus persister cells have increased survival to components of innate immunity, leading to persistence within a catheter-associated biofilm infection
Authors: Daubert Trevor Alan , Kluthe Kennedy , Nuxoll Austin 
Published: January 2023

Abstract
Staphylococcus aureus is known for its ability to cause chronic reoccurring infections in clinical settings. The organism’s ability to thrive despite antibiotic treatment has led to the severity of disease that is often exhibited with these infections. It has been hypothesized that energy-dependent persister formation leads to antibiotic tolerance in S. aureus. Persister cells are a dormant-like phenotypic variant of S. aureus that resemble cells growing in stationary phase. Previously, it was shown that a knockout in the tricarboxylic acid (TCA) cycle gene, fumC, which reduced intracellular ATP, led to an increase in the number of persisters. While persisters have been examined in relationship to antibiotic tolerance, it is currently unknown how persisters interact with the innate immune system. Considering a vast amount of chronic reoccurring infections in a clinical environment involve a biofilm, persisters were examined in a biofilm-associated catheter infection within a mouse. Following a 9 day infection, the fumC knockout exhibited increased survival within the tissue surrounding the catheter and within the heart compared to wild type S. aureus. Fluorescent activated cell sorting (FACS) analysis revealed similar recruitment of M1 and M2 macrophages, as well as neutrophils, suggesting there was not a difference in immunogenicity between the two strains. The fumC knockout exhibited increased survival compared to wild type S. aureus within a macrophage demonstrating persisters are better equipped to tolerate the innate immune system. These results indicate persisters are not only a problem with antibiotic treatment but are also better suited to survive the host’s immune system leading to increased survival within a host.
Screening of biological biomarker for distinguishing latent and active tuberculosis by proteome microarray
Authors: Li Chuanyou , Liu Yi 
Published: January 2023

Abstract
This study is to identify potential serum biomarkers for distinguishing between latent tuberculosis infection(LTBI) and active tuberculosis(ATB). A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum sample from patients with LTBI and ATB. The interaction network and functional classification of differentially expressed antigens were analyzed by STRING 10.0 and the TB datebase respectively. Enzyme-linked immunosorbent assays(ELISA) were used to validate candidate antigens further using 279 clinical samples. The diagnosis performances of candidate antigens were evaluated by receive operating characteristic curve(ROC) analysis. Both antigens combination and logistic regression analysis were used to improve diagnostic ability. Microarray results showed that levels of 152 Mycobacterium tuberculosis antigen-specific IgG were significantly higher in ATB patients than LTBI patients. These differentially expressed antigens showed stronger association each other and were involved in various biological processes. Eleven candidate antigens were further validated by ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher sensitivity and specificity for TB diagnosis. In addition, combination of both antigens and logistic regression analysis improved the diagnostic ability.
Dispensable role of chemokine receptors in migration of mycobacterial antigen-specific CD4+ T cells into mycobacteria-infected lung
Authors: Umemura Masayuki , Yamasaki Masatoshi , Tamura Toshiki , Matsuzaki Goro 
Published: January 2023

Abstract
Mycobacterial antigen-specific CD4+ Th1 cells have a pivotal role in protective immunity against mycobacterial infections, including pulmonary tuberculosis. In the course of infection, Th1 cells differentiate in the lung-draining lymph nodes and migrate into the infected lung. Chemokine receptors on T cells are involved in T cell migration into the intestine and skin. However, the role of chemokine receptors in the migration of CD4+ T cells into the lung has not yet been determined. To address this issue, the role of chemokine receptors in T cell migration into the mycobacteria-infected lung was analyzed using mycobacterial Ag85B peptide 25-specific T cell receptor-transgenic (P25) CD4+ T cells. P25 T cells in the Mycobacterium bovis BCG-infected lung and lung-draining mediastinal lymph nodes (MedLN) expressed the chemokine receptors, CCR5, CCR6, CXCR3, and CXCR5, which bind chemokines produced by the BCG-infected lung. To further analyze the role of chemokine receptors in the migration of BCG-primed P25 T cells into the lung and medLN, P25 T cells were adoptively transferred into BCG-infected wild-type mice and their migration into the lung was monitored. Unexpectedly, blocking chemokine receptor function with pertussis toxin, a G-protein inhibitor, failed to suppress migration of T cells into the infected lung. However, the treatment completely blocked migration of the MedLN P25 T cells into the recipient lymph node. These results suggest that the interaction of chemokine receptors on mycobacterial antigen-specific Th1 cells with chemokines is dispensable for their migration into the mycobacteria-infected lung.
Advancing Compensation into the Future with the Next Generation of Comp Beads
Authors: Calderon Veronica E , Montoya Leticia , Chen Yongfen , York Adam 
Published: January 2023

Abstract
A need for more robust compensation techniques comes with continued growth in the study of immunotherapy and immunology by flow cytometry. Compensation is a method used to address the measurement of a fluorophore in multiple detectors (referred to as spillover) by mathematically correcting signal overlap between emission spectra of different fluorochromes to determine the true level of staining/positive target signal. The signal spillover can impact data quality and becomes very important with different levels of marker expressions. This measurement can be achieved by use of cells, or more typically by use of compensation beads to save precious biological samples.
Current compensation beads have been shown to be problematic and can lead to over- or under-compensation, resulting in less or more true positive signal, respectively. Additionally, current compensation beads are incompatible with far red violet and ultraviolet dyes and may not be ideal for dim/low expressing markers.
These studies address compensation by comparing various compensation products to biological samples on multiple immunophenotyping panels of either human or murine origin. These panels compare the use of a wide range of fluorophore conjugates, including the use of violet and ultraviolet excitable dyes, low expressing targets, and intracellular targets to determine compensation accuracy. The results demonstrate that a precise compensation matrix can be obtained with a newly improved commercial bead that is comparable to a cell sample. This data validates that precious cell samples may not be needed to be used in place of commercial bead products to obtain accurate compensation and quality data regardless of a panel’s design elements.
Microfluidic generation of lipid nanoparticles to facilitate DNA entry into human mast cells
Authors: Kulka Marianna , Puga Narcy Arizmendi 
Published: January 2023

Abstract
Mast cells are highly granulated immune cells that can be targeted for transfection using lipid nanoparticles (LNP). Lipid nanoparticles (LNPs) were composed of cholesterol and 1-Stearoyl-2-oleoyl-sn-glycero-3-phosphocholine, the ionizable lipid 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane, and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] using microfluidic mixing and used to encapsulate a plasmid encoding enhanced green fluorescent protein (EGFP) under the control of a human cytomegalovirus promoter (pEGFP-C1). Encapsulation efficiency was determined using PicoGreen and LNP size was measured using dynamic light scattering. Human mast cells-1 (HMC-1) were transfected with loaded or empty LNPs in the presence or absence of apolipoprotein E (ApoE) for 24, 48 or 72 hours in medium. Cells were analyzed by fluorescence microscopy and flow cytometry. LNPs were approximately 100 nm in diameter (ideal) and efficiently encapsulated plasmids pEGFP-C1 (75.38%). ApoE4 appeared to slightly augment (&gt;10%) LNP uptake after 24 hr. Our study demonstrates that LNPs generated by microfluidic mixing efficiently encapsulate a plasmid payload and can be used to successfully transfect human mast cells. Carrier molecules such as ApoE can be used to augment LNP uptake by mast cells. Further functionalization and optimization of these LNPs can provide powerful new tools for targeting other immune cells.
A Performance-Optimized Multicolor Flow Cytometry Dried-Reagent Cocktail for Memory T-Cell Analysis
Authors: Hanley Mary , Bharadwaj Mamatha , Lomas Chip , Bornheimer Scott , Saksena Suraj , Afonina Elena , Lopes Erika Barboza Prado 
Published: January 2023

Abstract
The reliance on flow cytometry for phenotypical and functional analyses of immune components in both research and clinical laboratories has increased the need flow cytometric assay standardization. Dried-down reagent cocktails pre-optimized with regards to fluorophore choice for each specificity as well as concentration of each conjugate can improve standardization. Use of a pre-optimized dried-down cocktail provides an efficient assay workflow which can minimize operator error in addition to offering enhanced reagent stability and reduced variability across instruments and sites.
We developed a dried-down reagent cocktail for the identification and characterization of CD4+ and CD8+ T-cell memory and naïve subsets, including stem cell memory populations. The BD Horizon™ Dri Memory T cell panel contains optimized antibody-fluorophore conjugates against CD3, CD4, CD8, CD45RA, CD197, CD27 and CD95. Additional markers can be accommodated as drop-ins for a more comprehensive analysis.
This cocktail was optimized for stain index in all channels of a red, blue, violet laser flow cytometer (BD FACSLyric™) in liquid format, then converted to dry format. The performance of the dried-down cocktail, with regards to MFI and % positivity of T-cell subsets, is comparable to that of its optimized liquid equivalents. Additionally, results are consistent across FACSLyric instruments and similarly when acquired on a BD LSRFortessa™.
The comparable performance of the dried-down cocktail tube, along with the advantages offered by using a dried reagent cocktail, and the convenience of adding liquid drop-in reagents, reveal the BD Horizon Dri Memory T cell panel tube to be a valuable option for memory T-cell flow cytometry analysis.
Inhibition of CSF-1R curtails inflammation during experimental autoimmune encephalomyelitis
Authors: Hwang Daniel , Ciric Bogoljub 
Published: January 2023

Abstract
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are autoimmune diseases characterized by extensive infiltration of T cells and myeloid cells into the CNS. Treatments for MS are typically either non-specific immunosuppressive drugs or target adaptive immune cells. However, mounting evidence shows that myeloid cells have essential roles in MS/EAE pathology, but few, if any, MS drugs specifically target myeloid cells. A promising strategy for bridging this gap in treatment modalities for MS may be targeting CSF-1R, a receptor tyrosine kinase with important roles in myeloid cells, including survival and differentiation. We found that blocking CSF-1R signaling attenuated EAE and our analysis of the CNS these mice revealed substantially diminished numbers of inflammatory myeloid cells. These data demonstrate that inhibiting CSF-1R signaling is a viable strategy for attenuating myeloid cell responses during autoimmune neuroinflammation. These studies also suggest that targeting CSF-1R signaling may be an effective approach for treating MS.
Taurodeoxycholate, a master key locking both priming and activation signal necessary for inflammasomal activation of microglia by Amyloid beta in Alzheimer’s diseases
Authors: ISLAM MD JAHIRUL , Cho Jong-Ah , Kim Tae-Joo , Kim Bong Jik , Moon Sung-Yoon , Lee Eun-Young , Lee Song-Jin , Seong Seung-Yong 
Published: January 2023

Abstract
Alzheimer’s disease (AD) is an inflammatory neurodegenerative condition characterized by deposition of amyloid beta (Abeta) in the brain and origins dementia. Neuronal apoptosis following neuroinflammation by Abeta impairs cognition and memory. In this study we focused on Taurodeoxyxcholate (TDCA) is an active bile acid derivative with potent anti-inflammatory function.
In 5× Familial Alzheimer’s disease (5xFAD) mice model, chronic administration of TDCA in 5xFAD mice improved learning and memory in different memory test compared with PBS group. TDCA treatment significantly decreased neuronal apoptosis, load of Abeta plaques, the number of activated GFAP+ astrocytes and Iba-1+ microglia in different brain region of 5xFAD mice. CD11bhiGr1intF4/80+ myeloid cells in brain and spleen increased significantly in TDCA-treated group compared to PBS-treated group when brain single cell were immune-stained. In vitro, TDCA increased phagocytosis of Abeta. TDCA suppressed NLRP3-ASC oligomerization and production of mature IL-1β/IL-18 in Microglia by Abeta. TDCA inhibited Ca++ influx incurred by ATP or BzATP (P2X7 agonists). Compared with wild type, Ca++ influx of macrophages from TGR5 KO mice was like that of P2X7 KO mice in response to BzATP, suggesting that TDCA might play role as an inverse agonist for TGR5 complexed with P2X7. TDCA activates adenylate cyclase and cAMP inhibit priming phase of inflammasomal activation and oligomerization of NLRP3-ASC complex, suggesting that TDCA suppresses both priming and activation phase of NLRP3 inflammasome. TDCA and its novel chemical derivatives could be better choice in ameliorating broad spectrum of neuroinflammation to improve cognition and memory in AD patients.
Alpha-synuclein (αS) functions as an alarmin to promote inflammatory and immune responses by activating dendritic cells and macrophages
Authors: Alam Md Masud , Yang De , Li Xiao-Qing , Liu Jia , Back Timothy Carrel , Trivett Anna , Karim Baktiar , Zasloff Michael , Oppenheim Joost J 
Published: January 2023

Abstract
Alpha-synuclein (αS) is causally involved in the development of neurodegenerative disorders including Parkinson’s disease (PD). Recently, αS has been shown to be a chemotactic activator of phagocytes. Here, we report that αS is a critical mediator of inflammatory and immune responses. Treatment with αS activated human and mouse dendritic cells (DCs) and macrophages at both phenotypic and functional levels. αS treatment of DCs triggered the NF-κB signaling pathway and predominantly enhanced their Th1-polarizing capacity. αS also polarized mouse macrophages in an M1 direction. Activation of APCs by αS was mediated by TLR4. Intraperitoneal administration of αS recruited DCs and macrophages into the peritoneal cavity, while inflammatory reactions in the peritoneal cavity and colons induced αS expression and production. Importantly, immunization with ovalbumin (OVA) in the presence of αS promoted OVA-specific antibody and T cell responses, whereas the induction of inflammatory and OVA-specific immune responses was markedly reduced in αS−/− mice. Thus, αS can be considered an alarmin that functions as a mediator of inflammatory and immune responses. The potent proinflammatory and immunostimulating effects of αS in the periphery may cause the accumulation of αS and inflammatory damage in the central nervous system, culminating in Parkinson disease (PD).
Dimethyl Itaconate, an Itaconate Derivative, Exhibits Immunomodulatory Effects on Neuroinflammation in Experimental Autoimmune Encephalomyelitis
Authors: Kuo Ping-Chang , Weng Wen-Tsan , Scofield Barbara A. , Paraiso Hallel C. , Brown Dennis A. , Yu I-Chen , Yen Jui-Hung 
Published: January 2023

Abstract
Itaconate has recently emerged as a regulator of immune cell function. Studies show that itaconate is required for the activation of anti-inflammatory transcription factor Nrf2 by LPS in macrophages. Moreover, dimethyl itaconate (DMI), an itaconate derivative, has been shown to inhibit IL-17-induced IκBζ activation in keratinocytes and modulate IL-17-IκBζ pathway-mediated skin inflammation in an animal model of psoriasis. Currently, the effect of itaconate on regulating macrophage functions and peripheral inflammatory immune responses is well established. However, its effect on microglia (MG) and CNS inflammatory immune responses remains unexplored. Thus, in this study we investigated whether itaconate possesses an immunomodulatory effect on regulating MG activation and CNS inflammation in experimental autoimmune encephalomyelitis (EAE). Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced to assess the therapeutic effect of DMI. Our results show DMI ameliorated disease severity in the chronic C57BL/6 EAE model. Further analysis of the cellular and molecular mechanisms revealed that DMI mitigated blood-brain barrier disruption, inhibited MMP3 and MMP9 production, suppressed microglia activation, and repressed CNS infiltration of Th1 and Th17 cells. Strikingly, DMI also exhibited a therapeutic effect on lessening severity of relapse in the relapsing-remitting SJL/J EAE model. In conclusion, we demonstrate for the first time that DMI suppressed neuroinflammation and ameliorated disease severity in EAE through multiple cellular and molecular mechanisms, and our findings suggest that DMI can be developed as a novel therapeutic agent for the treatment of EAE through its anti-inflammatory properties.