KIRA6 is an Effective and Versatile Mast Cell Inhibitor of IgE‐mediated Activation. [[{“value”:”Veronika Wunderle, Thomas Wilhelm, Shatha Boukeileh, Jonas Goßen, Michael A. Margreiter, Roman Sakurov, Sandro Capellmann, Maike Schwoerer, Nabil Ahmed, Gina Bronneberg, Michel Arock, Christian Martin, Thomas Schubert, Francesca Levi‐Schaffer, Giulia Rossetti, Boaz Tirosh, Michael Huber”}]]

We discovered that the IRE1α−targeting small molecule KIRA6 is a potent inhibitor of the SRC family kinases LYN and FYN. Thereby it prevents mast cell activation by blocking the antigen-triggered activation of the high affinity IgE receptor FcεRI. Thus, KIRA6 is able to abolish mast cell-mediated allergic responses. ABSTRACT Mast cell (MC)-driven allergic diseases are … Read more

Distinct Tissue‐Dependent Composition and Gene Expression of Human Fetal Innate Lymphoid Cells. [[{“value”:”Inga E. Rødahl, Martin A. Ivarsson, Liyen Loh, Jeff E. Mold, Magnus Westgren, Danielle Friberg, Jenny Mjösberg, Niklas K. Björkström, Nicole Marquardt, Douglas F. Nixon, Jakob Michaëlsson”}]]

CD16+ and CD16− Natural Killer cells and type 3 innate lymphoid cells are found in early human development with distinct distribution and phenotype across fetal tissues. The presence of CD34+RORyt+Eomes± cells selectively in the fetal intestine indicates the presence of tissue-specific progenitors. ABSTRACT The human fetal immune system starts to develop in the first trimester … Read more

Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation. [[{“value”:”Stefanie Westermann, Daniel Radtke, Lisa Kramer, Stefan Wirtz, David Voehringer”}]]

Expression of constitutively active STAT6 in IECs of VillinCre_STAT6vt mice leads to enhanced pathology during DSS-induced colitis by regulation of genes involved in various functional pathways associated with epithelial barrier integrity in the colon. ABSTRACT Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) often associated with a Type 2 immune response. Although previous reports … Read more

Human Genetic GLUT1 Deficiency Results in Impaired T Cellular IFN‐γ Production. [[{“value”:”Renske de Jong, Anandhi Rajendiran, Judit Turyne Hriczko, Sudheendra Hebbar Subramanyam, Alina Rein, Martin Häusler, Thorsten Orlikowsky, Norbert Wagner, Daniel Erny, Kim Ohl, Klaus Tenbrock”}]]

GLUT1 deficiency prevents glucose uptake in T cells resulting in lower intracellular ATP generation and IFNy production.

SHIP‐1 Differentially Regulates IgE‐Induced IL‐10 and Antiviral Responses in Human Monocytes. [[{“value”:”Siva Kumar Solleti, Bailey E. Matthews, Jingyi Wu, Regina K. Rowe”}]]

IgE-mediated activation of human monocytes results in SHIP-1 activation, IL-10 production, and inhibition of antiviral IP-10. SHIP-1 inhibition by 3AC enhanced IL-10 but suppressed antiviral IP-10. This indicates differential regulatory roles for SHIP-1, which could impact antiviral responses in allergic diseases. ABSTRACT IgE-mediated stimulation of monocytes regulates multiple cellular functions including cellular maturation, cytokine release, … Read more

Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC. [[{“value”:”Diana Dudziak, Lukas Heger, William W Agace, Joyce Bakker, Tanja D. de Gruijl, Regine J. Dress, Charles‐Antoine Dutertre, Thomas M. Fenton, Marieke F. Fransen, Florent Ginhoux, Oded Heyman, Yael Horev, Florian Hornsteiner, Vinitha Kandiah, Paz Kles, Ruth Lubin, Gabriel Mizraji, Anastasia Prokopi, Or Saar, Sieghart Sopper, Patrizia Stoitzner, Helen Strandt, Martina M Sykora, Elisa C. Toffoli, Christoph H. Tripp, Kim van Pul, Rieneke van de Ven, Asaf Wilensky, Simon Yona, Claudia Zelle‐Rieser”}]]

We here provide detailed protocols for isolating single cell suspension from human nonlymphoid tissues, such as gingiva, lung, intestine, skin, and different tumor tissues as well as tumor-draining lymph nodes. Further, we provide gating strategies for flow cytometric analysis of human DC subpopulations in diverse nonlymphoid tissues. Abstract This article is part of the Dendritic … Read more

A Switch Protein Adapter for Anti‐LILRB4 CAR‐T Cells. [[{“value”:”Ryan Huang, Heyu Chen, Jingjing Xie, Qi Lou, Lingxiao Tan, Ningyan Zhang, Zhiqiang An, Samuel John, Cheng Cheng Zhang”}]]

Chimeric antigen receptor (CAR) T-cells have proven effective in hematologic malignancies targeting a restricted set of tumor-associated antigens. In this work, we demonstrate that CAR-T cells can be redirected to alternative tumor antigens through a switch protein adapter with antitumor efficacy in preclinical models. ABSTRACT Chimeric antigen receptor-T cell (CAR-T) immunotherapy has shown remarkable results … Read more

Dual Activation‐Induced Marker Combinations Efficiently Identify and Discern Antigen‐Specific and Bystander‐Activated Human CD4+ T Cells. [[{“value”:”Maria Grazia Ceraolo, Maristella Leccese, Antonino Cassotta, Sara Triolo, Mauro Bombaci, Elena Coluccio, Daniele Prati, Riccardo Ungaro, Sergio Abrignani, Alessandra Bandera, Federica Sallusto, Antonio Lanzavecchia, Samuele Notarbartolo”}]]

Identifying activated T lymphocytes and discerning antigen-specific from bystander T cells is crucial for understanding immune responses. Dual AIM combinations significantly enhance the ability to distinguish antigen-specific from bystander-activated T cells compared with single AIMs. They also have a better positive predictive value and specificity with a modest reduction in sensitivity. ABSTRACT Identifying activated T … Read more

Tumor‐Expressed SPPL3 Supports Innate Antitumor Immune Responses. [[{“value”:”Tamara Verkerk, Antonius A. de Waard, Sofie J. I. Koomen, Jasper Sanders, Tineke Jorritsma, Anouk T. Pappot, Nordin D. Zandhuis, Tao Zhang, Manfred Wuhrer, Arie J. Hoogendijk, Floris P. J. van Alphen, Maartje van den Biggelaar, Hannes S. J. Stockinger, Klaas P. J. M. van Gisbergen, Robbert M. Spaapen, S. Marieke van Ham”}]]

Tumor and immune cells interact through receptor–ligand interactions. B3GNT5 produces nsGSL on tumor cells which is regulated by SPPL3. When SPPL3 is absent, elevated nsGSL levels hinder receptor–ligand binding, leading to reduced immune cell activation. ABSTRACT The development of an effective antitumor response relies on the synergistic actions of various immune cells that recognize tumor … Read more

Tviblindi algorithm identifies branching developmental trajectories of human B‐cell development and describes abnormalities in RAG‐1 and WAS patients. [[{“value”:”Marina Bakardjieva, Ondřej Pelák, Marjolein Wentink, Hana Glier, David Novák, Jitka Stančíková, Daniela Kužílková, Ester Mejstříková, Iga Janowska, Marta Rizzi, Mirjam van der Burg, Jan Stuchlý, Tomáš Kalina”}]]

Novel computational framework tviblindi identifies branching B cell developmental trajectories in healthy (HD) and abnormal (RAG-1 and Wiskott–Aldrich syndrome primary immunodeficiency) bone marrow and peripheral blood samples using 30 parameter mass cytometry. Integrated vaevictis projection allows interpretation of trajectories to κ (grey arrow) and λ (black arrow) light chain expressing B cells, memory development branching … Read more

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