bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory and Stimulatory Effects of IL-32 on HIV-1 Infection
Authors: Nasser Hesham , Takahashi Naofumi , Eltalkhawy Youssef M , Reda Omnia , Lotfi Sameh , Nasu Kanako , Sakuragi Jun-ichi , Suzu Shinya 
Published: October 2022

Abstract
The proinflammatory cytokine IL-32 is elevated in the plasma and tissues of HIV-1–infected individuals. However, its significance in HIV-1 infection remains unclear because IL-32 inhibits and stimulates viral production in monocyte-derived macrophages (MDMs) and CD4+ T cells, respectively. In this study, we initially found that the inhibitory effect on human MDMs depends on SAMHD1, a dNTP triphosphohydrolase that inhibits viral reverse transcription. IL-32 increased the unphosphorylated active form of SAMHD1, which was consistent with the reduced expression of the upstream cyclin-dependent kinases. Indeed, IL-32 lost its anti–HIV-1 activity in MDMs when SAMHD1 was depleted. These results explain why IL-32 inhibits HIV-1 in MDMs but not CD4+ T cells, because SAMHD1 restricts HIV-1 in noncycling MDMs but not in cycling CD4+ T cells. Another unique feature of IL-32 is the induction of the immunosuppressive molecule IDO1, which is beneficial for HIV-1 infection. In this study, we found that IL-32 also upregulates other immunosuppressive molecules, including PD-L1, in MDMs. Moreover, IL-32 promoted the motility of MDMs, which potentially facilitates intercellular HIV-1 transmission. Our findings indicate that IL-32 has both the direct inhibitory effect on HIV-1 production in MDMs and the indirect stimulatory effects through phenotypic modulation of MDMs, and they suggest that the stimulatory effects may outweigh the inhibitory effect because the window for IL-32 to inhibit HIV-1 is relatively confined to SAMHD1-mediated reverse transcription suppression in the viral life cycle.
Identification of HLA-E Binding Mycobacterium tuberculosis–Derived Epitopes through Improved Prediction Models
Authors: Ruibal Paula , Franken Kees L M C , van Meijgaarden Krista E , van Wolfswinkel Marjolein , Derksen Ian , Scheeren Ferenc A , Janssen George M C , van Veelen Peter A , Sarfas Charlotte , White Andrew D , Sharpe Sally A , Palmieri Fabrizio , Petrone Linda , Goletti Delia , Abeel Thomas , Ottenhoff Tom H M , Joosten Simone A 
Published: October 2022

Abstract
Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, posing great social and economic burden to affected countries. Novel vaccine approaches are needed to increase protective immunity against the causative agent Mycobacterium tuberculosis (Mtb) and to reduce the development of active TB disease in latently infected individuals. Donor-unrestricted T cell responses represent such novel potential vaccine targets. HLA-E-restricted T cell responses have been shown to play an important role in protection against TB and other infections, and recent studies have demonstrated that these cells can be primed in vitro. However, the identification of novel pathogen-derived HLA-E binding peptides presented by infected target cells has been limited by the lack of accurate prediction algorithms for HLA-E binding. In this study, we developed an improved HLA-E binding peptide prediction algorithm and implemented it to identify (to our knowledge) novel Mtb-derived peptides with capacity to induce CD8+ T cell activation and that were recognized by specific HLA-E-restricted T cells in Mycobacterium-exposed humans. Altogether, we present a novel algorithm for the identification of pathogen- or self-derived HLA-E-presented peptides.
Casting a Wide NET
Authors: Kaplan Mariana J 
Published: October 2022

Abstract
This Pillars of Immunology article is a commentary on “Neutrophil extracellular traps kill bacteria,” a pivotal article written by V. Brinkmann, U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann, D. S. Weiss, Y. Weinrauch, and A. Zychlinksy, and published in Science, in 2004. https://www.science.org/doi/10.1126/science.1092385. The Journal of Immunology, 2022, 209: 843–844.
Molecular Basis for the Recognition of HIV Nef138-8 Epitope by a Pair of Human Public T Cell Receptors
Authors: Ma Keke , Chai Yan , Guan Jiawei , Tan Shuguang , Qi Jianxun , Kawana-Tachikawa Ai , Dong Tao , Iwamoto Aikichi , Shi Yi , Gao George F 
Published: October 2022

Abstract
Cross-recognized public TCRs against HIV epitopes have been proposed to be important for the control of AIDS disease progression and HIV variants. The overlapping Nef138-8 and Nef138-10 peptides from the HIV Nef protein are HLA-A24–restricted immunodominant T cell epitopes, and an HIV mutant strain with a Y139F substitution in Nef protein can result in immune escape and is widespread in Japan. Here, we identified a pair of public TCRs specific to the HLA-A24–restricted Nef-138-8 epitope using PBMCs from White and Japanese patients, respectively, namely TD08 and H25-11. The gene use of the variable domain for TD08 and H25-11 is TRAV8-3, TRAJ10 for the α-chain and TRBV7-9, TRBD1*01, TRBJ2-5 for the β-chain. Both TCRs can recognize wild-type and Y2F-mutated Nef138-8 epitopes. We further determined three complex structures, including TD08/HLA-A24-Nef138-8, H25-11/HLA-A24-Nef138-8, and TD08/HLA-A24-Nef138-8 (2F). Then, we revealed the molecular basis of the public TCR binding to the peptide HLA, which mostly relies on the interaction between the TCR and HLA and can tolerate the mutation in the Nef138-8 peptide. These findings promote the molecular understanding of T cell immunity against HIV epitopes and provide an important basis for the engineering of TCRs to develop T cell–based immunotherapy against HIV infection.
NPAT Supports CD8+ Immature Single-Positive Thymocyte Proliferation and Thymic Development
Authors: Cui Zejin , Zhao Fan , Chen Xiaoping , Li Jiahui , Jin Xuexiao , Han Yongmei , Wang Lie , Zhou Yiting , Lu Linrong 
Published: October 2022

Abstract
Thymocytes need to proliferate into a significant cell mass to allow a subsequent selection process during the double-positive (DP) stage. However, it is not clear at what stage this massive cell proliferation occurs. Immature CD8 single-positive (ISP) cells are a well-defined thymocyte subpopulation. However, the function of this cell subset has not yet been characterized. In this study, we analyzed the transcription pattern of mouse ISP cells and observed higher expression levels of cell cycling genes. We also found out that ISP cells exhibited the highest cell proliferative capacity among thymocytes in different developmental stages. Nuclear protein ataxia-telangiectasia (NPAT/p220) is one of the highly expressed cell cycling genes in ISP cells, which is known to play a critical role in coordinating histone gene expression necessary for rapid cell proliferation. Selective deletion of NPAT at the ISP stage led to reduced thymus size and significant loss of DP cells, secondary to reduced histone gene expression and impaired ISP cell proliferation capacity. A block of thymocyte development at the ISP stage was also observed, which was due to increased IL-7R expression. Continuous IL-7R signal served as a compensating mechanism for cell proliferation upon NPAT deletion, but in turn inhibited the expression of transcription factors TCF-1 and LEF-1, which is essential for the transition of ISP to DP cells. In summary, our study revealed the proliferation capacity of the ISP subpopulation during thymocyte differentiation as well as a vital role of NPAT in this developmental stage.
Deficiency of p53 Causes the Inadequate Expression of miR-1246 in B Cells of Systemic Lupus Erythematosus
Authors: Zhang Qing , Liu Yu , Liao Jieyue , Wu Ruifang , Zhan Yi , Zhang Peng , Luo Shuangyan 
Published: October 2022

Abstract
Underexpression of p53 is considered the leading cause of the decreased miR-1246 expression in B cells of systemic lupus erythematosus (SLE) patients, yet the exact mechanism of action still remains unclear. To further explore the molecular mechanism of p53 upregulating miR-1246 expression, we targeted the methylation and acetylation of histone H3 in the miR-1246 promoter region of SLE B cells. We found that increased histone H3 trimethylation at Lys27 (H3K27me3) and decreased histone H3 acetylation at Lys9 and Lys14 (H3K9/K14ac) in the miR-1246 promoter region are essential for the low expression of miR-1246 in SLE B cells. p53 can promote miR-1246 transcription by recruiting Jumonji domain–containing protein 3 (JMJD3), E1A-binding protein p300 (EP300), and CREB-binding protein (CBP) to bind to the miR-1246 promoter, downregulating H3K27me3 and upregulating H3K9/K14ac. Furthermore, early B cell factor 1 (EBF1), CD40, CD38, and X box binding protein-1 (XBP-1) expression levels in SLE B cells transfected with p53 expression plasmid were significantly decreased, whereas autoantibody IgG production in autologous CD4+ T cells cocultured with overexpressed p53 SLE B cells was reduced. Collectively, our data suggest that the reduction of p53 decreases miR-1246 expression via upregulation of H3K27me3 and downregulation of H3K9/14ac, which in turn results in SLE B cell hyperactivity.
Cutting Edge: The Expression of Transcription Inhibitor GFI1 Is Induced by Retinoic Acid to Rein in Th9 Polarization
Authors: Friesen Leon , Kostlan Raymond , Liu Qingyang , Yu Hao , Zhu Jinfang , Lukacs Nicholas , Kim Chang H 
Published: October 2022

Abstract
IL-9, produced mainly by specialized T cells, mast cells, and group 2 innate lymphoid cells, regulates immune responses, including anti-helminth and allergic responses. Polarization of naive CD4 T cells into IL-9–producing T cells (Th9s) is induced by IL-4 and TGF-β1 or IL-1β. In this article, we report that the transcription factor growth factor–independent 1 transcriptional repressor (GFI1) plays a negative role in mouse Th9 polarization. Moreover, the expression of GFI1 is controlled by liganded RARα, allowing GFI1 to mediate the negative effect of retinoic acid on IL-9 expression. The Gfi1 gene has multiple RARα binding sites in the promoter region for recruiting nuclear coactivator steroid receptor coactivator-3 and p300 for histone epigenetic modifications in a retinoic acid–dependent manner. Retinoic acid–induced GFI1 binds the Il9 gene and suppresses its expression. Thus, GFI1 is a novel negative regulator of Il9 gene expression. The negative GFI1 pathway for IL-9 regulation provides a potential control point for Th9 activity.
Immune Subtypes and Immune Landscape Analysis of Endometrial Carcinoma
Authors: Liang Leilei , Zhu Yunshu , Li Jian , Zeng Jia , Yuan Guangwen , Wu Lingying 
Published: October 2022

Abstract
Some patients with endometrial cancer (EC) suffer from limited survival benefits after immunotherapy, suggesting that there may be a specific pattern associated with immunotherapy. Immune-related genes were extracted from The Cancer Genome Atlas databases. We analyzed the differences among immune subtypes (ISs) in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, immune checkpoint-related genes, immunotherapy, and chemotherapy. We applied dimensionality reduction and defined the immune landscape of EC. Then, we used the Weighted Gene Co-Expression Network Analysis package to identify the coexpression modules of these immune genes. Finally, hub genes were selected and detected by quantitative PCR and immunohistochemistry. We obtained three ISs. There were differences in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, and immune checkpoint–related genes among the ISs. Regarding immunotherapy and chemotherapy, the IS2 subtypes were more sensitive to programmed cell death protein 1 inhibitors. In addition, different positions in the immune landscape map exhibited different prognostic characteristics, providing further evidence of the ISs. The IS2 subtypes were significantly positively correlated with yellow module gene list, indicating a good prognosis with high score. SIRPG and SLAMF1 were identified as the final characteristic genes. The quantitative PCR and immunohistochemistry results showed that the expression levels of SIRPG and SLAMF1 were low in human EC tissue. In this study, we identified three reproducible ISs of EC. The immune landscape analysis further revealed the intraclass heterogeneity of the ISs. SIRPG and SLAMF1 were identified to be associated with progression, suggesting that they may be novel immune-related biomarkers of EC.
Breaking the Paradigm: Selection of Self-Reactive Natural Antibodies
Authors: Baumgarth Nicole 
Published: October 2022

Abstract
This Pillars of Immunology article is a commentary on “Positive Selection of Natural Autoreactive B Cells,” a pivotal article written by K. Hayakawa, M. Asano, S. A. Shinton, M. Gui, D. Allman, C. L. Stewart, J. Silver, and R. R. Hardy, and published in Science, in 1999. https://doi.org/10.1126/science.285.5424.113.
Immune Responses to SARS-CoV-2 in Pregnancy: Implications for the Health of the Next Generation
Authors: Shook Lydia L , Fourman Lindsay T , Edlow Andrea G 
Published: October 2022

Abstract
Widespread SARS-CoV-2 infection among pregnant individuals has led to a generation of fetuses exposed in utero, but the long-term impact of such exposure remains unknown. Although fetal infection is rare, children born to mothers with SARS-CoV-2 infection may be at increased risk for adverse neurodevelopmental and cardiometabolic outcomes. Fetal programming effects are likely to be mediated at least in part by maternal immune activation. In this review, we discuss recent evidence regarding the effects of prenatal SARS-CoV-2 infection on the maternal, placental, and fetal immune response, as well as the implications for the long-term health of offspring. Extrapolating from what is known about the impact of maternal immune activation in other contexts (e.g., obesity, HIV, influenza), we review the potential for neurodevelopmental and cardiometabolic morbidity in offspring. Based on available data suggesting potential increased neurodevelopmental risk, we highlight the importance of establishing large cohorts to monitor offspring born to SARS-CoV-2–positive mothers for neurodevelopmental and cardiometabolic sequelae.
Single-Cell Immunobiology of the Maternal–Fetal Interface
Authors: Miller Derek , Garcia-Flores Valeria , Romero Roberto , Galaz Jose , Pique-Regi Roger , Gomez-Lopez Nardhy 
Published: October 2022

Abstract
Pregnancy success requires constant dialogue between the mother and developing conceptus. Such crosstalk is facilitated through complex interactions between maternal and fetal cells at distinct tissue sites, collectively termed the “maternal–fetal interface.” The emergence of single-cell technologies has enabled a deeper understanding of the unique processes taking place at the maternal–fetal interface as well as the discovery of novel pathways and immune and nonimmune cell types. Single-cell approaches have also been applied to decipher the cellular dynamics throughout pregnancy, in parturition, and in obstetrical syndromes such as recurrent spontaneous abortion, preeclampsia, and preterm labor. Furthermore, single-cell technologies have been used during the recent COVID-19 pandemic to evaluate placental viral cell entry and the impact of SARS-CoV-2 infection on maternal and fetal immunity. In this brief review, we summarize the current knowledge of cellular immunobiology in pregnancy and its complications that has been generated through single-cell investigations of the maternal–fetal interface.
Natural Antibodies Alert the Adaptive Immune System of the Presence of Transformed Cells in Early Tumorigenesis
Authors: Rawat Kavita , Soucy Shannon M , Kolling Fred W , Diaz Kiara Manohar , King William T , Tewari Anita , Jakubzick Claudia V 
Published: October 2022

Abstract
Recent studies have revealed a critical role for natural Abs (NAbs) in antitumor immune responses. However, the role of NAbs in cancer immunosurveillance remains unexplored, mainly because of the lack of in vivo models that mimic the early recognition and elimination of transforming cells. In this article, we propose a role for NAbs in alerting the immune system against precancerous neoantigen-expressing cells immediately after they escape intrinsic tumor suppression mechanisms. We identify four distinct reproducible, trackable, MHC-matched neoantigen-expressing cell models that do not form tumors as the end point. This amplified readout in the critical window prior to tumor formation allows investigation of new mediators of cancer immunosurveillance. We found that neoantigen-expressing cells adoptively transferred in NAb-deficient mice persisted, whereas they were eliminated in wild-type mice, indicating that the circulating NAb repertoire alerts the immune system to the presence of transformed cells. Moreover, immunity is mounted against immunogenic and nonimmunogenic neoantigens contained in the NAb-tagged cells, regardless of whether the NAb directly recognizes the neoantigens. Beyond these neoantigen-expressing model systems, we observed a significantly greater tumor burden in chemically and virally induced tumor models in NAb-deficient mice compared with wild-type mice. Restoration of the NAb repertoire in NAb-deficient mice elicited the recognition and elimination of neoantigen-expressing cells and cancer. These data show that NAbs are required and sufficient for elimination of transformed cells early in tumorigenesis. These models can now be used to investigate how NAbs stimulate immunity via recognition receptors to eliminate precancerous cells.
PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality
Authors: Pandian Nagakannan , Kanneganti Thirumala-Devi 
Published: October 2022

Abstract
Innate immunity is the first response to protect against pathogens and cellular insults. Pattern recognition receptors sense pathogen- and damage-associated molecular patterns and induce an innate immune response characterized by inflammation and programmed cell death (PCD). In-depth characterization of innate immune PCD pathways has highlighted significant cross-talk. Recent advances led to the identification of a unique inflammatory PCD modality called PANoptosis, which is regulated by multifaceted PANoptosome complexes that are assembled by integrating components from other PCD pathways. The totality of biological effects observed in PANoptosis cannot be accounted for by any other PCD pathway alone. In this review, we briefly describe mechanisms of innate immune cell death, including molecular mechanisms of PANoptosis activation and regulation. We also highlight the PANoptosomes identified to date and provide an overview of the implications of PANoptosis in disease and therapeutic targeting. Improved understanding of innate immune-mediated cell death, PANoptosis, is critical to inform the next generation of treatment strategies.
Nhận xét các trường hợp cắt tử cung hoàn toàn sau LEEP tại Bệnh viện Phụ sản Trung ương
Authors: Phạm Huy Hiền Hào , Vũ Đình Tuấn , Nguyễn Quang Minh 
Published: October 2022

Mục tiêu: Mô tả đặc điểm lâm sàng và cận lâm sàng của bệnh nhân cắt tử cung hoàn toàn sau LEEP tại Bệnh viện Phụ sản Trung ương.
Đối tượng và phương pháp nghiên cứu: Nghiên cứu hồi cứu trên 51 bệnh nhân bệnh nhân được cắt tử cung hoàn toàn sau LEEP tại Bệnh viện Phụ Sản Trung ương, từ tháng 1 năm 2017 đến tháng 12 năm 2020.
Kết quả: Xét nghiệm tế bào cổ tử cung bình thường và ASCUS, LSIIL có 95,65% tổn thương mô bệnh học từ CIN-II trở lên, kết quả sinh thiết chỉ phát hiện ra 19,6% trường hợp CIN-III và 3,92 ung thư cổ tử cung. Trong khi đó, khi làm LEEP phát hiện 64,92% ung thư cổ tử cung (19,6 CIN-III, 45,06 CIS và 19,6% ung thư xâm nhập). Trên bệnh phẩm cắt tử cung, có 3,92% CIN-III, 27,45% ung thư cổ tử cung (13,73% CIS, 1,96% AIS, 11,76% ung thư cổ tử cung xâm nhập).
Kết luận: Xét nghiệm tế bào cổ tử cung trong những trường hợp tế bào bình thường, ASCUS và LSIL không tương ứng với tổn thương mô bệnh học; LEEP phát hiện tổn thương ung thư cổ tử cung cao hơn so với sinh thiết; tỷ lệ tổn thương nặng trên bệnh phẩm cắt tử cung thấp, nhưng tổn thương mức độ càng cao thì còn tồn tại sau điều trị LEEP càng tăng.
Ứng dụng kỹ thuật array CGH trong chẩn đoán trước sinh một số bất thường nhiễm sắc thể tại Bệnh viện Phụ sản Hà Nội
Authors: Đinh Thúy Linh , Hoàng Hải Yến , Phạm Thế Vương , Trần Thị Minh Thu , Nguyễn Đức Nghĩa , Nguyễn Tài Đức , Nguyễn Duy Ánh 
Published: October 2022

Trong chẩn đoán trước sinh các bất thường nhiễm sắc thể (NST), kỹ thuật nuôi cấy tế bào ối hiện vẫn là tiêu chuẩn vàng. Tuy nhiên, chỉ phát hiện được các bất thường với kích thước > 5 Mb (trên 5 triệu cặp Base). Kỹ thuật array CGH (Microarray-based comparative genomic hybridization) có khả năng đánh giá trên toàn bộ 24 NST giúp phát hiện các bất thường mất cân bằng của NST bao gồm các trường hợp lệch bội, mất hoặc nhân đoạn của NST. Hơn nữa, kỹ thuật array CGH cho phép phát hiện các bất thường của NST ngay cả khi không có định hướng trong chẩn đoán.
Mục tiêu: Xác định tỷ lệ bất thường một số nhiễm sắc thể qua kỹ thuật array CGH tại Bệnh viện Phụ sản Hà Nội.
Đối tượng, phương pháp nghiên cứu: 306 thai phụ có tuổi thai 17 - 28 tuần có chỉ định chọc hút nước ối tại Bệnh viện Phụ sản Hà Nội từ 10/2020 - 09/2021, mẫu nước ối được thực hiện đồng thời 2 kỹ thuật: array CGH và nuôi cấy tế bào ối.
Kết quả: Kỹ thuật karyotype phát hiện được 35/306 (11,4%) bất thường nhiễm sắc thể, trong khi đó array CGH phát hiện được 51/306 (16,7%). Array CGH phát hiện 25 trường hợp bất thường lệch bội, tương đương karyotype. Với các bất thường mất đoạn/nhân đoạn lớn, kỹ thuật array phát hiện được 9 trường hợp, trong khi đó karyotype phát hiện được 8 trường hợp; với các mất đoạn/nhân đoạn nhỏ, array CGH phát hiện được 16 trường hợp trong khi karyotype chỉ phát hiện được 1 trường hợp.
Kết luận: Array CGH là xét nghiệm có độ chính xác cao, phát hiện được các trường hợp bất thường cấu trúc nhiễm sắc thể ở mức độ mất đoạn/nhân đoạn nhỏ mà kỹ thuật karyotype không phát hiện được.
Đặc điểm lâm sàng, cận lâm sàng thai phụ nhiễm SARS-CoV-2 tại Bệnh viện Phụ sản Trung ương và Bệnh viện Nhiệt đới Trung ương
Authors: Trần Danh Cường , Đặng Công Việt , Lê Chí Quang , Đặng Quang Hùng , Nguyễn Thị Thu Hà , Nguyễn Quốc Khánh 
Published: October 2022

Đặt vấn đề: Tổ chức Y tế thế giới đã công bố đại dịch toàn cầu do coronavirus 2019 (COVID-19) vào tháng 3 năm 2020. Kể từ đó, dịch bệnh đã phát triển nhanh chóng và lan rộng ra khắp thế giới, virus xâm nhập vào tất cả các đối tượng, mọi độ tuổi, kể cả phụ nữ có thai. Chẩn đoán, xử trí và tiên lượng thai phụ nhiễm SARS-CoV-2 có ý nghĩa quan trọng. Mục tiêu: Mô tả đặc điểm lâm sàng, cận lâm sàng của các thai phụ nhiễm SARS-CoV-2 tại Bệnh viện Phụ sản Trung ương và Bệnh viện Nhiệt Đới Trung ương.
Đối tượng: Những thai phụ nhập viện và được chẩn đoán nhiễm SARS-CoV-2 tại Bệnh viện Phụ sản Trung ương và Bệnh viện Nhiệt Đới Trung ương từ tháng 12/2021 đến tháng 2/2022.
Phương pháp: Nghiên cứu mô tả tiến cứu.
Kết quả: Tuổi trung bình của thai phụ trong nghiên cứu là 30,65 ± 6,00; trong đó nhóm tuổi 20 - 34 chiếm tỷ lệ cao nhất (71,67%). Tuổi thai trung bình trong nghiên cứu là 31,97 ± 6,98 tuần. Đa số (85%) các thai phụ nhiễm SARS-CoV-2 trong nghiên cứu chưa được tiêm vaccin. Triệu chứng nhiễm SARS-CoV-2 thường gặp nhất ở thai phụ trong nghiên cứu là ho (76,67%), sốt (55%) và khó thở (36,67%). Đa số thai phụ nhiễm SARS-CoV-2 trong nghiên cứu có tăng giá trị CRP (78,9%) và tăng D-Dimer (94,82%) tại thời điểm nhập viện.
Kết luận: Các thai phụ nhiễm SARS-CoV-2 trong nghiên cứu có ít nhất một triệu chứng lâm sàng: ho, sốt, khó thở. Các thai phụ nhiễm SARS-CoV-2 có xu hướng tăng giá trị CRP và D-Dimer máu.