bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Heard immunity”-pandemic teaches immunology vocabulary through hearing from news and social media outlets.
Authors: Fazal Nadeem , Brehm Danielle , Alakbarova Gulgaz , Cebiyev Nihat , Meher Satish , De Herde Laura 
Published: January 2023

Abstract
COVID-19 surprised the world and brought with it free immunology lessons. Ever since the pandemic news broke, the public were bombarded with immunological vocabulary. Immunology as a biomedical science had never attained student interest, let alone having an overwhelming global attention among the general public. The purpose of our study was to evaluate the extent to which immunology had become a common knowledge because of the main stream media and social outlets broadcasting news. We conducted a global survey of all people, regardless of gender identity, age, education, and geographical location to ask if they knew the meanings of specific immunological terms used in mainstream news outlets and social media. The words included, but were not limited to, antigen, antibody, T-cell, B-cell, mRNA, DNA, coronavirus, quarantine, lockdown, social distancing, PCR, rapid antigen tests, outbreak, herd immunity, vaccine, viral infections, infection rate, mortality rate, immunotherapy, and immune boosting drugs, etc. When we analyzed the data, we found the following trends. 139/179 (77.7%) said ’yes’, they did learn about immunology in lockdown. 100/179 (55.9%) said they learnt about Pfizer, followed by Moderna (33.5%), BioNTech (31.8%), and AstraZeneca (29.6%). 86/179 (48%) learnt about the body’s defense system, while 20.7% of people already knew about T cells, B cells, immune therapy, and immunity. 95/179 (53.1%) of people asked learned about airborne infections, making them the most common type of respiratory infections learnt about during COVID-19. The word ‘pandemic’ was learnt by 111/179 (62%) people. Overall, COVID-19 has propelled immunology into the general public’s vocabulary and knowledge in a way that has never been done before.
Designing a successful K-12 education program aimed to prevent infectious disease
Authors: Jarvi Susan Irene , Howe Kathleen , Brewer Francis , Baker Wendy 
Published: January 2023

Abstract
Developing collaborative efforts to train K-12 teachers and students as community educators is a strategy that is useful in preventing disease. The current pandemic illuminates the need for a greater focus on immunology and public health in K-12 STEM/STEAM education. The components of a course design and delivery impact success. University of Hawaii, Daniel K. Inouye College of Pharmacy’s Jarvi Lab, in collaboration with non-profits and professional educators, offers a for-credit, Professional Development Education course to Hawaii K-12 teachers using a curriculum focusing on rat lungworm disease, a debilitating and sometimes lethal disease caused by the parasite Angiostrongylus cantonensis. The PDE course is place-based; learning is centered on the local environment and in the community. It is taught online, allowing for statewide participation. The lessons are research-driven and standards-based. Parasite-host interactions, and disease presentation, treatment and prevention are emphasized. Course participants are provided access to peer-reviewed papers, educational videos, and webinars, which can be used in the classroom and support diverse learning styles. Participation in live (on-line) discussions with scientists and researchers help advance teacher understanding of the scientific methodology and study designs. Hands-on activities focus on modeling, data collection and analysis, and communication skills. Citizen Science, Design Thinking, and ArcGIS story mapping are introduced. Lessons encourage student-led inquiry and teamwork. Teachers’ final portfolios reflect the knowledge gained, their reviews of the course are positive, and they report a high level of student interest.
Supported by Hawaii State Legislature, Daniel K. Inouye College of Pharmacy
Strength of CAR signaling reveals bifurcation of T and ILC2 lineage differentiation from pluripotent stem cells
Authors: Li Suwen , Wang Chloe S , Montel-Hagen Amélie , Casero David , Lopez Shawn , Chen Ho-Chung , Zhou Olivia , Botero Carlos , Tsai Steven C , Wong Claudia , Crooks Gay M , Seet Christopher S 
Published: January 2023

Abstract
T cells and type 2 innate lymphoid cells (ILC2) are two closely related lymphoid lineages that share certain developmental and transcriptional programs, including a requirement for Notch and IL-7 signaling during differentiation. We recently developed an artificial thymic organoid (ATO) system that supports in vitro differentiation of human pluripotent stem cells (PSCs) to mature αβT cells. We show here that lentiviral introduction of a CD19-targeted chimeric antigen receptor (CAR) into PSCs surprisingly resulted in ILC2-biased lymphopoiesis from PSCs at the expense of T cell differentiation. PSC-derived ILC2s expressed the classical ILC2 markers CD25, CD200R, and CRTH2 as well GATA3, ID2, and TCF7, and responded to both cytokine stimuli and antigen-dependent CAR signaling by producing IL-5 and IL-13. To understand CAR-mediated lineage diversion from T to ILC2, we performed single cell RNAseq of PSC-derived hematopoietic progenitor cells before the phenotypic onset of either T or ILC2 differentiation. This revealed a gene signature of T cell receptor signaling, suggesting aberrant CAR activation at the earliest stages of lymphocyte development. We established that CAR signaling in ATOs was antigen-independent and thus likely driven by tonic signaling. We applied this finding to rationally modulate the T/ILC2 lineage decision by fine-tuning CAR signaling strength during lymphocyte development from PSCs, permitting restoration of conventional CAR-T cell differentiation or, conversely, directed differentiation of isogenic antigen-specific CAR-ILC2s. Taken together, our findings shed light on human ILC2 development and inform the applied differentiation of both ILC2s and conventional CAR-T cells from PSCs.
Supported by Tobacco-Related Disease Research Program Predoctoral Award (SL), Broad Stem Cell Research Center UCLA Fellowship (SL, CSS), CIRM Bridges Program (CB), NIH T32 (ST), NIH K08CA235525 (CSS).
Proteogenomic immune signatures delineate the landscape of pediatric acquired demyelinating syndromes
Authors: Espinoza Diego A , Mexhitaj Ina , Smiler Jacqueline , Mafra Fernanda , Da Silva Renata Pellegrino , Fadda Giulia , Yeh E Ann , Marrie Ruth Ann , Arnold Douglas L , Li Rui , Banwell Brenda , Bar-Or Amit 
Published: January 2023

Abstract
Approximately 20–30% of children presenting with acquired inflammatory demyelinating syndromes (ADS) have multiple sclerosis (MS). Another 30% harbor serum antibodies against myelin oligodendrocyte glycoprotein and are referred to as having MOG-associated disease (MOGAD). While MS and MOGAD can have similar features, differences in response to immune therapies point to distinct underlying immune mechanisms.
To assess potentially distinct immune mechanisms underlying MS and MOGAD, we applied proteogenomics to high quality cryopreserved peripheral blood mononuclear cells collected from patients with ADS prior to institution of immune therapy, as well as from healthy controls. CITE-Seq profiling was applied to a total of 92,716 single cells with equal contribution from 24 children (6 healthy donors; 6 with ADS but neither MS or MOGAD; 6 with MOGAD; and 6 with MS, ascertained with long-term follow-up).
Analysis revealed a pan-ADS enrichment of atypical (CD11c+) B cells compared to healthy controls. Children with MS were distinguished from children with MOGAD by MS-specific enrichments of checkpoint-molecule (TIGIT and CD137)-expressing CD8 memory T cells, STAT4+ Th1 CD4 memory T cells and CD56dim/CD16+ NK cells.
Overall, our study identifies distinct features of circulating cellular immune profiles that may serve to distinguish children with MS and MOGAD, and provides novel insights into early immune mechanisms that may be involved in each of these conditions.
T Cell Responses In Children With Asthma Against SARS-CoV-2 Correlates To Asthmatic Outcomes
Authors: Eyoh Enwono , Murrell Amelie , Werthmann Derek , Trinh Ivy , Stone Addison , Chandra Sruti , Elliott Debra , Smira Ashley , Velazquez Jalene V , Schieffelin John S , Kolls Jay K , Robinson James , Gunn Bronwyn M , Rabito Felicia , Norton Elizabeth B 
Published: January 2023

Abstract
SARS CoV-2 in children or special populations post-infection has not been well studied. Asthma is a heterogenous disease marked by chronic airway inflammation; triggers include cockroaches (CRA), and other inhaled irritants. Asthma also has links to viral infections like respiratory syncytial virus (RSV). Additionally, some with moderate to severe asthma are more likely to be hospitalized with COVID. T cells play key roles in asthma and control of viruses such; however, there is limited information connecting T cell responses in people with asthma to viral infections. We aimed to evaluate T cells and antibodies in an asthma confirmed cohort. Thirty-five children aged 5–17 years were included. We measured SARS CoV-2 spike (S) and Nucleoprotein (N) plasma antibody responses or effector functions and CD4, CD8 T cells specific to CRA or peptide pools made from RSV, S and N antigen using an activation induced markers (AIM) assay. Surprisingly, in this population many CD4 and CD8 T-cell AIM responses to S, N, CRA, and RSV were significantly associated, particularly for CD8 T-cells (Spearmans r = 0.57–0.76) and the restimulation antigens CRA and RSV. N-specific CD4 AIM was the only immune measure to correlate to a recent asthma attack within a month of the blood collection visit, though anti-N antibodies, CD4 AIM to CRA, RSV or CD8 AIM to CRA, RSV, or N antigens also correlated with asthmatic outcomes (e.g., ER visits, night waking from symptoms, etc.) whereas allergen specific IgE or anti-S IgG did not. Taken together these results indicate an immunological association between viral infection and asthma, broadly allowing for the conjecture that viral infections, in particular RSV and SARS-CoV-2 could act together as possible triggers of asthma.
Aiolos supports TFH cell differentiation by antagonizing the IL-2/STAT5 signaling pathway
Authors: Read Kaitlin , Pokhrel Srijana , Jones Devin M , Saadey Abbey , Eisele Caprice , Warren Robert T , Collins Patrick , Ghoneim Hazem E , Freud Aharon , Oestreich Kenneth J 
Published: January 2023

Abstract
CD4+ T follicular helper (TFH) cells are critical for the generation of robust humoral immune responses, as they provide help to B cells to support the generation of both pathogen-neutralizing antibodies and long-lived plasma cell populations. To date, the mechanisms underlying TFH differentiation are incompletely understood. Here, we identify the transcription factor Aiolos as a key regulator of TFH responses. We find that Aiolos expression is increased in TFH cell populations generated during influenza infection and that Aiolos deficiency results in compromised TFH cell differentiation and B cell helper activity. Mechanistically, loss of Aiolos results in diminished expression of TFH genes, including those encoding the key transcription factors Bcl-6, TCF-1, and Tox. Conversely, expression of genes associated with IL-2/STAT5 signaling, a known antagonist of the TFH gene program, were significantly elevated in Aiolos-deficient settings. Consistent with these data, antigen-specific Aiolos-deficient effector CD4+ T cell populations generated in response to influenza infection exhibited significantly elevated IL-2Rα surface expression. Together, our findings suggest that repression of IL-2/STAT5 signaling represents a novel mechanism by which Aiolos regulates the TFH gene program. These findings are important, as they provide critical insight that may ultimately be leveraged for the development of novel TFH-focused immunotherapies and strategies to improve vaccination approaches.
Supported by a grant from the NIAID (NIH; R01 AI134972), funds through The Ohio State University College of Medicine, and funds through The Ohio State University College of Medicine Advancing Research in Infection and Immunity Fellowship Program
Antimicrobial Peptide and Lipid Response of Alveolar Type II Model Cells to Cytokines of TH17 Signature
Authors: Toscano Cindy Lizette , Wesley-Cardwell India , Abou Abbas Dana A , Dzul Janette , Martinez Erik , Porter Edith 
Published: January 2023

Abstract
Mycobacterium tuberculosis (Mtb) causes ~ 10 million deaths each year worldwide. The current BCG vaccine that targets TH1 cells and anti-tuberculosis drugs have limited efficacy. Novel preventative measures are in dire need. Epithelial cells in the lungs are among the first host cells to encounter inhaled Mtb. Epithelial cells produce antimicrobial peptides (AMPs) like human beta-defensins (HBDs) and antimicrobial lipids (AMLs). Microbial products such as lipopolysaccharide (LPS), IL-1β made by macrophages, and IL-17 and IL-22 secreted by TH17 cells are all known to increase production of AMPs in epithelial cells. However, their effect on the production of AMLs is unknown. We hypothesized that TH17 cytokines increase the production of AMPs and AMLs in lung alveolar type II cells, leading to increased antimycobacterial activity. As determined by immunofluorescence, IL-17 combined with IL-22 (IL-17/22) significantly increased intracellular HBD2 in A549 cells after 48 h. Using the lipid sensitive fluoroprobes Bodipy and Nile Red, we found that IL-1β combined with LPS significantly increased intracellular neutral lipids, while IL-17/22, IL-1β/LPS, and LPS alone significantly increased neutral and polar lipid secretion after 24h stimulation. To assess the antimycobacterial effect of A549 secretions, we developed a qPCR-based assay employing Mycolicibacterium smegmatis (Ms), an avirulent model organism for Mtb, bacterial cell lysis with TRI reagent and bead beating, gDNA extraction with Direct-zol™ DNA Miniprep, SYBR Green chemistry, and 16S rRNA gene targeting primers, and testing is ongoing. This research may lead to novel vaccine approaches for Mtb based on TH17-induced antimycobacterial activity of lung epithelial cells.
This research was supported by NIH R25GM061331, NIH T34GM08228, and CalStateLA Provost’s Research Restart Grant.
Time course scRNAseq analysis on host mucosal immune responses to influenza virus infection during aging
Authors: Wu Yue , Tang Jinyi , Gao Xiaochen , Li Chaofan , Zhu Bibo , Zhang Ruixuan , Fain Cori , Ayasoufi Katayoun , Johnson Aaron J , Dong Haidong , Sun Jie 
Published: January 2023

Abstract
Aging has been shown to be one of the major risk factors for host morbidity and mortality following infections with respiratory viruses including influenza virus and SARS-CoV-2. The unique immune properties of the aged hosts not only influence pathogen clearance and tissue damage responses, but also modulate the pathogenesis of the long-term sequalae post acute viral clearance. Currently, the dynamics and features of mucosal immune responses following acute respiratory viral infections in the aged hosts remain to be fully elucidated. Here, we characterized the lung cellular and molecular profiles following influenza virus infection in young (~3-month-old) or aged (~24-month-old) mice with a chronological manner from acute to chronic phase. Using DNA-oligo-conjugated CD45 antibody and i.v. labeling, we were able to distinguish the unique responses of circulating vs lung-resident immune cells to influenza virus infection during aging. These responses were further validated by spectral flow cytometry analysis of the lung innate and adaptive immune cells. Further data analysis and integration are warranted for this unique large data set detailing the single cell molecular profiles of mucosal responses to influenza virus infection comparing young and aged hosts.
Epithelial-derived oxysterol production tunes intestinal IgA secretion against commensals and enteric pathogen in tissue
Authors: Ceglia Simona , Berthelette Alyssa , Howley Kelsey , Li Yun , Yiew Nicole K H , Xu Ying , Brink Robert Adrian , Cyster Jason G , Hooper Lora V , Randolph Gwendalyn J , Reboldi Andrea 
Published: January 2023

Abstract
Immunoglobulin A (IgA) secretion by plasma cells (PCs), terminally differentiated B cells residing in the intestinal lamina propria, assures microbiome homeostasis and protects the host against enteric infections. However, whether exposure to diet-derived and commensal-derived signals instruct tissue resident PCs effector function and dynamically shape IgA immune responses at the mucosal barrier remain largely uninvestigated. Here, we demonstrated that intestinal epithelial cells (IECs) integrate luminal input to produce 7α,25-dihydroxycholesterol (7α,25-HC), a cholesterol metabolite (oxysterol) with immunomodulatory functions. In IECs, both cholesterol uptake via NPC1L1 and commensal recognition via MyD88 controlled oxysterol production. Mice lacking the oxysterol enzyme CH25H specifically in IECs abolished 7α,25-HC production and allowed to study oxysterol generation and activity in the small intestine. Inability of IECs to generate 7α,25-HC enhanced IgA secretion by PCs in the gut, suggesting that oxysterol negatively regulate humoral response at the mucosal barriers. Mechanistically, we showed that intestinal PCs sensed 7α,25-HC via the chemoattractant receptor GPR183 to position in the lamina propria tissue. This IEC-PC axis was rapidly modulated by cholesterol dietary content and tuned Salmonella-specific IgA response.
Our finding revealed a new mechanism linking dietary cholesterol and humoral immune responses centered around PC localization for efficient mucosal protection.
Supported by grants from Kenneth Rainin Foundation, Innovator Award, Charles H. Hood Foundation Child Health Research Awards Program, The Leukemia and Lymphoma Society New Idea Award and the Multiple Myeloma Research Fellowship, NIH (AI40098) and The American Association of Immunologists Careers in Immunology Fellowship Program.
Increased tryptase expression in HαT is associated with upregulation of epithelia-derived MRGPRX2 agonists and MRGPRX2+ MCs in the GI mucosa
Authors: Glover Sarah C , Williams Haley , Pride Yilianys , Owings Anna H , Robinson Tanya , Lyons Jonathan , Deepak Vishwa , Ali Hydar 
Published: January 2023

Abstract
Hereditary α-tryptasemia (HαT) is a genetic trait characterized by elevated serum tryptase and increased copy number of the TPSAB1 gene. It is associated with flushing, itching, GI symptoms and anaphylaxis. HαT gut epithelia undergo increased rates of pyroptosis, and HαT gut mast cells (MCs) are increased in number with highly expressed FCER1 and CD203C. Gut MCs express Mas-related G protein–coupled receptor-X2 (MRGPRX2). Studies have clearly shown that this receptor contributes to host defense, mediates pseudo-allergy, and is involved in a number of atopic skin conditions. Herein, we sought to evaluate the impact of MRGPRX2 in individuals with HαT and GI symptoms. We observed increased numbers of MRGPRX2+ mast cells in HαT versus non-HαT gastrointestinal (GI) biopsies (colon-&gt;duodenum-&gt;stomach-&gt;Ileum). mRNA expression of tryptase and MRGPRX2 in intestine of HαT increased ~6-fold and 3-fold respectively over non-HαT biopsies. Epithelial derived agonists of MGPRX2 including human beta defensin (HBD) 2 and adrenomedullin (PAMP12) mRNA expression were also found to be upregulated ~2-fold and ~3-folds in HαT over non-HαT biopsies. MC protease carboxydeptidase-3 was also increased. Taken together, this data suggests that in addition to upregulation of MRGPRX2 in MCs, increased tryptase expression in HαT leads to upregulation of MRGPRX2 agonists and modifiers in gut epithelial cells, nociceptors and MCs, and results in GI symptoms.
This work was supported by National Institutes of Health grants R01-AI124182, R01-AI143185 and R01-AI149487 to Hydar Ali.
Genetically knock out of PSGL-1 increases CD19-CAR-T cells persistence in mouse pre-B-ALL disease model
Authors: Mavuluri Jayadev 
Published: January 2023

Abstract
Chimeric antigen receptor T cell therapy is reported as a fifth pillar of cancer therapy. CAR-T therapy has success against DLBCL’s. Although it is an effective cancer treatment, CAR-T cells still faces challenges like persistence and exhaustion. P selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like selectin counter receptor on T-cells that binds to P-selectin, E-selectin, and L-selectin on endothelial cells. In our study, we observed CRISPR-Cas9 knockout of P-Selectin Glycoprotein Ligand-1(PSGL-1) in human Pan-T cells showed increased persistence by enhancing the anti-apoptotic pathway and further reduces the exhaustion by reduced expression of PD-1, TIM3 and LAG3. Hence PSGL-1 can be used as a potential target in the reprogramming of CAR T-cells and successful CAR T-cell therapy might be achieved with a smaller number of infusions to the patients. Our preclinical study in B6 mouse model, pre-B-ALL disease model clearly shows PSGL-1 KO CD19-CAR-T cells, effectively clears the tumors, persist for longer time by maintain the central memory phenotype and having lower exhaustion profile. GSEA pathway enrichment analysis from RNA seq of PSGL-1 KO CD19 CAR-T cells shows PSGL-1 KO CD19-CAR-T cells has central memory phenotype and lower exhaustion profile, further confirmed by immunophenotyping these PSGL1-KO CD19-CAR-T cells. From our study, it is evident that PSGL-1 KO CAR-T cells can overcome the limitations of CAR-T cells hurdles like maintaining the central memory phenotype and lower exhaustion In summary, our study is clear evident that PSGL-1 KO CAR-T cells can be used as universal CAR-T system to target all kind tumors not limiting to hematological cancers.
Leveraging mouse genetics to generate heavy-chain only antibodies for therapeutic application
Authors: Borbet Timothy C , Perault Andrew , Ilmain Juliana , Chan Kun-Wei , Luo Christina C , Bryan Arielle M , Kirilov Milen , Wang Wei , Sheiffele Paul , Kong Xiang-Peng , Ekiert Damian , Torres Victor , Koralov Sergei B 
Published: January 2023

Abstract
Conventional antibodies (Abs) consist of two heavy and two light immunoglobulin chains, while heavy-chain only antibodies (HCAbs), like those found in camelid and shark species, are unique because they lack a light chain binding partner. The unique structure of these HCAbs impart advantageous properties to these smaller Abs, including greater accessibility to their target antigens, higher hydrophilicity, and greater conformational stability under environmental stresses. We have generated a mouse model, the IgG3dCH1 strain, that can produce HCAbs from the endogenous murine heavy chain locus. We have shown that these mice undergo efficient B cell development in the bone marrow, and generate a diverse repertoire of B cells that populate all peripheral immune compartments. While single-cell sequencing analysis of B cells revealed some biases in VH and JH usage, it also highlighted the tremendous diversity of rearrangements that give rise to B cells bearing these single chain antibodies. We’ve been able to show that upon immunization, IgG3dCH1 animals are protected from lethal bacterial challenge with a pathogenic strain of Enterobacter hormaechei and generate pathogen specific IgG. Further, immunization with SARS-CoV2 stabilized prefusion spike protein elicited HCAbs with a KD in the nM range, measured via bio-layer interferometry. These data support this mouse being utilized as a platform for the generation of pathogen-specific HCAbs that can be further engineered for testing and application for translational outcomes.
Supported by grants from NIH (T32 AI007180, R43 AI136141).