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JOURNAL ARTICLE
Duygu Uzun-Goren, Yesim Hulya Uz
OBJECTIVES: We aimed to investigate the effects of quercetin (QRC) against cyclophosphamide (CP)-induced testicular damage and how it interacts with apoptotic and inflammatory signaling pathways. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided into four groups, 10 in each group; Control group (corn oil, intragastrically, 14 days), QRC group (100 mg/kg QRC, dissolved in corn oil, 14 days), CP group (200 mg/kg CP, intraperitoneally, single dose on the 7th day), and CP+QRC group (100 mg/kg QRC, intragastrically, 14 days and 200 mg/kg CP, intraperitoneally, single dose on the 7th day)...
2024: Iranian Journal of Basic Medical Sciences
#2
JOURNAL ARTICLE
Jillian A Bristol, Scott E Nelson, Makoto Ohashi, Alejandro Casco, Mitchell Hayes, Erik A Ranheim, Abigail S Pawelski, Deo R Singh, Daniel J Hodson, Eric C Johannsen, Shannon C Kenney
Epstein-Barr virus (EBV) is an important cause of human lymphomas, including Burkitt lymphoma (BL). EBV+ BLs are driven by Myc translocation and have stringent forms of viral latency that do not express either of the two major EBV oncoproteins, EBNA2 (which mimics Notch signaling) and LMP1 (which activates NF-κB signaling). Suppression of Myc-induced apoptosis, often through mutation of the TP53 (p53) gene or inhibition of pro-apoptotic BCL2L11 (BIM) gene expression, is required for development of Myc-driven BLs...
April 15, 2024: PLoS Pathogens
#3
JOURNAL ARTICLE
Christine Nguyen, Matthew Kudek, Ryan Zander, Hongshen Niu, Jian Shen, Ashley Bauer, Donia Alson, Achia Khatun, Yao Chen, Jie Sun, William Drobyski, Brian T Edelson, Weiguo Cui
In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice...
April 15, 2024: Journal of Immunology
#4
JOURNAL ARTICLE
Arijita Jash, Thomas Pridmore, James B Collins, Ariel M Hay, Krystalyn E Hudson, Chance John Luckey, James C Zimring
Administration of anti-RhD immunoglobulin (Ig) to decrease maternal alloimmunization (antibody-mediated immune suppression [AMIS]) was a landmark clinical development. However, IgG has potent immune-stimulatory effects in other settings (antibody-mediated immune enhancement [AMIE]). The dominant thinking has been that IgG causes AMIS for antigens on RBCs but AMIE for soluble antigens. However, we have recently reported that IgG against RBC antigens can cause either AMIS or AMIE as a function of an IgG subclass...
April 15, 2024: Journal of Clinical Investigation
#5
JOURNAL ARTICLE
Rocío Pastor, Juliana Puyssegur, M Paula de la Guardia, Lindybeth Sarmiento Varón, Gladys Beccaglia, Nicolás Spada, Andrea Paes de Lima, M Soledad Collado, Andrés Blanco, Isabel Aspe Scetti, M Elena Arabolaza, Bibiana Paoli, Fernando Chirdo, Eloísa Arana
BACKGROUND: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells...
April 12, 2024: Immunity & Ageing: I & A
#6
JOURNAL ARTICLE
Hirotsugu Oda, Kalpana Manthiram, Pallavi Pimpale Chavan, Eva Rieser, Önay Veli, Öykü Kaya, Charles Rauch, Shuichiro Nakabo, Hye Sun Kuehn, Mariël Swart, Yanli Wang, Nisa Ilgim Çelik, Anne Molitor, Vahid Ziaee, Nasim Movahedi, Mohammad Shahrooei, Nima Parvaneh, Nasrin Alipour-Olyei, Raphael Carapito, Qin Xu, Silvia Preite, David B Beck, Jae Jin Chae, Michele Nehrebecky, Amanda K Ombrello, Patrycja Hoffmann, Tina Romeo, Natalie T Deuitch, Brynja Matthíasardóttir, James Mullikin, Hirsh Komarow, Jennifer Stoddard, Julie Niemela, Kerry Dobbs, Colin L Sweeney, Holly Anderton, Kate E Lawlor, Hiroyuki Yoshitomi, Dan Yang, Manfred Boehm, Jeremy Davis, Pamela Mudd, Davide Randazzo, Wanxia Li Tsai, Massimo Gadina, Mariana J Kaplan, Junya Toguchida, Christian T Mayer, Sergio D Rosenzweig, Luigi D Notarangelo, Kazuhiro Iwai, John Silke, Pamela L Schwartzberg, Bertrand Boisson, Jean-Laurent Casanova, Seiamak Bahram, Anand Prahalad Rao, Nieves Peltzer, Henning Walczak, Najoua Lalaoui, Ivona Aksentijevich, Daniel L Kastner
The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpin leads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members...
April 12, 2024: Nature Immunology
#7
JOURNAL ARTICLE
Alina K Lorant, Anna E Yoshida, Emily A Gilbertson, Talyn Chu, Caroline Stefani, Mridu Acharya, Jessica A Hamerman, Adam Lacy-Hulbert
Plasmacytoid dendritic cells (pDCs) are strongly implicated as a major source of IFN-I in systemic lupus erythematosus (SLE), triggered through TLR-mediated recognition of nucleic acids released from dying cells. However, relatively little is known about how TLR signaling and IFN-I production are regulated in pDCs. In this article, we describe a role for integrin αvβ3 in regulating TLR responses and IFN-I production by pDCs in mouse models. We show that αv and β3-knockout pDCs produce more IFN-I and inflammatory cytokines than controls when stimulated through TLR7 and TLR9 in vitro and in vivo...
April 12, 2024: Journal of Immunology
#8
JOURNAL ARTICLE
Emily Dennis, Maria Murach, Cassidy M R Blackburn, Melissa Marshall, Katherine Root, Tanyaporn Pattarabanjird, Justine Deroissart, Loren D Erickson, Christoph J Binder, Stefan Bekiranov, Coleen A McNamara
Recent studies have demonstrated a role for Ten-Eleven Translocation-2 (TET2), an epigenetic modulator, in regulating germinal center formation and plasma cell differentiation in B-2 cells, yet the role of TET2 in regulating B-1 cells is largely unknown. Here, B-1 cell subset numbers, IgM production, and gene expression were analyzed in mice with global knockout of TET2 compared to wildtype (WT) controls. Results revealed that TET2-KO mice had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow (B-1a) and spleen (B-1b)...
2024: Frontiers in Immunology
#9
JOURNAL ARTICLE
Fatimah Budair, Naotomo Kambe, Toshiaki Kogame, Masahiro Hirata, Riko Takimoto-Ito, Alshimaa Mostafa, Takashi Nomura, Kenji Kabashima
Antibody-secreting cells (ASCs) produce immunoglobulin (Ig) G and IgE autoantibodies in secondary lymphoid organs. Evidence also suggests their existence in the skin in various chronic inflammatory conditions, and in association with CXCL12 and CXCL13, they regulate the recruitment/survival of ASCs and germinal center formation to generate ASCs, respectively. However, the presence of IgG and IgE in bullous pemphigoid (BP) lesions needs to be addressed. Here, we aimed to analyse BP skin for the presence of IgG and IgE and the factors contributing to their generation, recruitment, and persistence...
April 2024: Experimental Dermatology
#10
Hu Zeng, Xingxing Zhu, Yue Wu, Yanfeng Li, Xian Zhou, Jens Watzlawik, Yin Chen, Ariel Raybuck, Daniel Billadeau, Virginia Shapiro, Wolfdieter Springer, Sun Jie, Mark Boothby
During the humoral immune response, B cells undergo rapid metabolic reprogramming with a high demand for nutrients, which are vital to sustain the formation of the germinal centers (GCs). Rag-GTPases sense amino acid availability to modulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway and suppress transcription factor EB (TFEB) and transcription factor enhancer 3 (TFE3), members of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, how Rag-GTPases coordinate amino acid sensing, mTORC1 activation, and TFEB/TFE3 activity in humoral immunity remains undefined...
March 29, 2024: Research Square
#11
JOURNAL ARTICLE
Ming Zhao, Chunting He, Xueyun Zheng, Min Jiang, Zhiqiang Xie, Hongjiao Wei, Shujun Zhang, Ying Lin, Jiaheng Zhang, Xun Sun
Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers...
April 3, 2024: Journal of Controlled Release
#12
JOURNAL ARTICLE
Lingling Zhang, Amparo Toboso-Navasa, Arief Gunawan, Abdouramane Camara, Rinako Nakagawa, Katja Finsterbusch, Probir Chakravarty, Rebecca Newman, Yang Zhang, Martin Eilers, Andreas Wack, Pavel Tolar, Kai-Michael Toellner, Dinis Pedro Calado
The transition from immunoglobulin M (IgM) to affinity-matured IgG antibodies is vital for effective humoral immunity. This is facilitated by germinal centers (GCs) through affinity maturation and preferential maintenance of IgG+ B cells over IgM+ B cells. However, it is not known whether the positive selection of the different Ig isotypes within GCs is dependent on specific transcriptional mechanisms. Here, we explored IgG1+ GC B cell transcription factor dependency using a CRISPR-Cas9 screen and conditional mouse genetics...
April 5, 2024: Science Immunology
#13
JOURNAL ARTICLE
Xinyu Chen, Jingrong Liu, Amanda Juan Chen, Lin Wang, Xianzhi Jiang, Andong Gong, Wende Liu, Hanxiang Wu
BACKGROUND: Maize stalk rot (MSR) caused by Fusarium graminearum is the primary factor contributing to the reduction in maize yield and quality. However, this soil-borne disease is challenging to control in agriculture through field management and the use of chemical agents. The process of screening novel biocontrol agents can aid in the creation of innovative and successful MSR control strategies. RESULTS: A total of 407 strains of bacteria were isolated from the rhizosphere soil of a resistant maize inbred line...
April 5, 2024: Pest Management Science
#14
REVIEW
Aina Akmal Mohd Noor, Abdah Karimah Che Md Nor, Norhanani Mohd Redzwan
The development of psoriasis is mainly driven by the dysregulation of T cells within the skin, marking a primary involvement of these cells in the pathogenesis. Although B cells are integral components of the immune system, their role in the initiation and progression of psoriasis is not as pivotal as that of T cells. The paradox of B cell suggests that, while it is crucial for adaptive immunity, B cells may contribute to the exacerbation of psoriasis. Numerous ideas proposed that there are potential relationships between psoriasis and B cells especially within germinal centers (GCs)...
April 5, 2024: Journal of Cellular Physiology
#15
JOURNAL ARTICLE
Jie Li, Christopher R Chin, Hsia-Yuan Ying, Cem Meydan, Matthew R Teater, Min Xia, Pedro Farinha, Katsuyoshi Takata, Chi-Shuen Chu, Yiyue Jiang, Jenna Eagles, Verena Passerini, Zhanyun Tang, Martin A Rivas, Oliver Weigert, Trevor J Pugh, Amy Chadburn, Christian Steidl, David W Scott, Robert G Roeder, Christopher E Mason, Roberta Zappasodi, Wendy Béguelin, Ari M Melnick
Despite regulating overlapping gene enhancers and pathways, CREBBP and KMT2D mutations recurrently co-occur in germinal center (GC) B cell-derived lymphomas, suggesting potential oncogenic cooperation. Herein, we report that combined haploinsufficiency of Crebbp and Kmt2d induces a more severe mouse lymphoma phenotype (vs either allele alone) and unexpectedly confers an immune evasive microenvironment manifesting as CD8+ T-cell exhaustion and reduced infiltration. This is linked to profound repression of immune synapse genes that mediate crosstalk with T-cells, resulting in aberrant GC B cell fate decisions...
April 3, 2024: Nature Communications
#16
JOURNAL ARTICLE
Mustafa Akkoyunlu
Like the other invasive encapsulated bacteria, Streptococcus pneumoniae is also covered with a polysaccharide structure. Infants and elderly are most vulnerable to the invasive and noninvasive diseases caused by S. pneumoniae . Although antibodies against polysaccharide capsule are efficient in eliminating S. pneumoniae , the T cell independent nature of the immune response against polysaccharide vaccines renders them weakly antigenic. The introduction of protein conjugated capsular polysaccharide vaccines helped overcome the weak immunogenicity of pneumococcal polysaccharides and decreased the incidence of pneumococcal diseases, especially in pediatric population...
December 31, 2024: Human Vaccines & Immunotherapeutics
#17
JOURNAL ARTICLE
Iqra R Kasu, Octavio Reyes-Matte, Alejandro Bonive-Boscan, Alan I Derman, Javier Lopez-Garrido
UNLABELLED: Spores of Bacillus subtilis germinate in response to specific germinant molecules that are recognized by receptors in the spore envelope. Germinants signal to the dormant spore that the environment can support vegetative growth, so many germinants, such as alanine and valine, are also essential metabolites. As such, they are also required to build the spore. Here we show that these germinants cause premature germination if they are still present at the latter stages of spore formation and beyond, but that B...
April 2, 2024: MBio
#18
Claudio Tripodo, Valeria Cancila, Gaia Morello, Giorgio Bertolazzi, Allison Si-Yu Chan, Giulia Bastianello, Daniel Paysan, Patrick William Jaynes, Giovanna Schiavoni, Fabrizio Mattei, Silvia Piconese, Maria Revuelta, Francesco Noto, Adele De Ninno, Ilenia Cammarata, Fabio Pagni, Saradha Venkatachalapathy, Sabina Sangaletti, Arianna Di Napoli, Davide Vacca, Silvia Lonardi, Luisa Lorenzi, Andrés J M Ferreri, Beatrice Belmonte, Gabriele Varano, Mario Paolo Colombo, Silvio Bicciato, Giorgio Inghirami, Leandro Cerchietti, Maurilio Ponzoni, Roberta Zappasodi, Fabio Facchetti, Marco Foiani, Stefano Casola, Anand D Jeyasekharan
The germinal center (GC) dark zone (DZ) and light zone (LZ) regions spatially separate expansion and diversification from selection of antigen-specific B-cells to ensure antibody affinity maturation and B cell memory. The DZ and LZ differ significantly in their immune composition despite the lack of a physical barrier, yet the determinants of this polarization are poorly understood. This study provides novel insights into signals controlling asymmetric T-cell distribution between DZ and LZ regions. We identify spatially-resolved DNA damage response and chromatin compaction molecular features that underlie DZ T-cell exclusion...
March 18, 2024: Research Square
#19
JOURNAL ARTICLE
Filipa Marques Rodrigues, Mariana Santos, Ricardo Martins
BACKGROUND Primary central nervous system diffuse large B-cell lymphoma (DLBCL) is an extremely aggressive brain disease that rarely affects immunocompetent non-elderly patients, particularly with hemorrhagic presentation. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of this entity, which typically demonstrates restricted diffusion and a T2 hypointense appearance, suggesting hypercellularity. CASE REPORT A 44-year-old man came to the emergency department with a persistent and treatment-resistant bilateral frontal headache that had been bothering him for the past 3 weeks...
April 2, 2024: American Journal of Case Reports
#20
JOURNAL ARTICLE
Dan Xiong, Chengjie Geng, Liyi Zeng, Hua Yao, Jiewen Tan, Lan Zhang, Xiaohui Liu, Langxia Liu
Diffuse Large B-cell lymphoma (DLBCL) is a highly aggressive disease with heterogeneous outcomes and marked variability in the response to chemotherapy. DLBCL comprises two major subtypes: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC). Our study highlights the extensive antitumour activity of artesunate (ART) against both major DLBCL subtypes. Transcriptome analysis suggests the potential involvement of ferroptosis in artesunate-induced cell death. Because of low glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with the accumulation of free iron (Fe2+ ), artesunate induces the excessive production of reactive oxygen species (ROS), ultimately leading to ferroptosis, a form of cell death driven by phospholipid peroxidation...
April 15, 2024: Heliyon
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