European Journal of Immunology

RAG1/2 induces double‐stranded DNA breaks at non‐Ig loci in the proximity of single sequence repeats in developing B cells. [[{“value”:”Katarina Ochodnicka‐Mackovicova, Michal Mokry, Martin Haagmans, Ted E. Bradley, Carel J.M. van Noesel, Jeroen E.J. Guikema”}]]

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RAG1/2 endonuclease induces off-target DNA breaks in developing B cells, highlighting its genotoxic potential beyond the immunoglobulin loci. This genome-wide study in mouse pre-B cells identifies RAG1/2-dependent DSBs and uncovers their predominant association with GA and CA dinucleotide repeats and GC-rich motifs, providing new insights into RAG1/2-targeting. Abstract In developing B cells, V(D)J gene recombination … Read more

Regulation of IFN‐γ production by ZFP36L2 in T cells is time‐dependent. [[{“value”:”Nordin D. Zandhuis, Aurélie Guislain, Abeera Popalzij, Sander Engels, Branka Popović, Martin Turner, Monika C. Wolkers”}]]

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We uncovered a novel time-dependent role for the RNA-binding protein ZFP36L2 in regulating IFN-γ production. ZFP36L2 was redundant in regulating cytokine production during early T-cell activation. However, upon continued T-cell activation, ZFP36L2 dampens the production of IFN-γ by binding to AU-rich elements in the 3ʹUTR and promoting mRNA degradation. Abstract CD8+ T cells kill target … Read more

Functional Fc receptors are crucial in antibody‐mediated protection against cytomegalovirus. [[{“value”:”Anna Bootz, Nina Reuter, Falk Nimmerjahn, William J. Britt, Michael Mach, Thomas H. Winkler”}]]

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The mechanisms of protection of therapeutically applied antibodies in cytomegalovirus infection are so far unknown. Here it is shown in an in vivo mouse model that Fc-receptors are essential for protection from a lethal infection in immunodeficient hosts. Whereas NK cells have a limited role, monocytes are involved in protection. Created with BioRender.com. Abstract Human … Read more

Site‐specific serology unveils cross‐reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes. [[{“value”:”Philipp C. G. Paparoditis, Alexander Fruehwirth, Kajetana Bevc, Jun Siong Low, Josipa Jerak, Laura Terzaghi, Mathilde Foglierini, Blanca Fernandez, David Jarrossay, Davide Corti, Federica Sallusto, Antonio Lanzavecchia, Antonino Cassotta”}]]

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The authors developed a novel blocking of binding (BoB)-ELISA to accurately estimate the titers of serum antibodies targeting distinct influenza hemagglutinin (HA) epitopes. Leveraging BoB-ELISA, the authors found that serum antibodies targeting the HA head epitopes were immunodominant, whereas antibodies against the stem epitope, although subdominant, were highly prevalent in healthy donors. Importantly, BoB-ELISA allowed … Read more

A20 intrinsically influences human effector T‐cell survival and function by regulating both NF‐κB and JNK signaling. [[{“value”:”Gina Dabbah‐Krancher, Allison Ruchinskas, Melissa A. Kallarakal, Katherine P. Lee, Bradly M. Bauman, Benjamin Epstein, Hongli Yin, Daniel Krappmann, Brian C. Schaefer, Andrew L. Snow”}]]

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The ubiquitin-editing enzyme A20 regulates innate and adaptive immune receptor signaling, but its intrinsic function in human T cells is poorly understood. We show that A20 deletion enhances cytokine secretion and alters apoptosis sensitivity in primary human T cells by modulating NF-kB and JNK/AP-1 signaling downstream of the CARD11-BCL10-MALT1 complex. Abstract A20 is a dual-function … Read more

Chronic stimulation desensitizes β2‐adrenergic receptor responses in natural killer cells. [[{“value”:”Martin Jürgens, Maren Claus, Sabine Wingert, Jens Alexander Niemann, Lea Katharina Picard, Elisabeth Hennes, Ina Haasler, Birte Hellwig, Nina Overbeck, Jörg Reinders, Jörg Rahnenführer, Michaela Schedel, Silvia Capellino, Carsten Watzl”}]]

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β2-adrenergic receptor (β2AR) stimulation of NK cells inhibits inside-out signaling and LFA-1 activation, explaining the mobilization of NK cells upon acute stress. Repeated or sustained β2AR stimulation desensitizes β2AR via G-protein switch. Local administration of long-acting β2-agonists does not interfere with systemic NK cell functions in asthma patients. Abstract Adrenergic receptors (ARs) are preferentially expressed … Read more

Liver type 1 innate lymphoid cells undergo apoptosis in murine models of macrophage activation syndrome and are dispensable for disease. [[{“value”:”Amber De Visscher, Marte Vandeput, Jessica Vandenhaute, Bert Malengier‐Devlies, Eline Bernaerts, Kourosh Ahmadzadeh, Jessica Filtjens, Tania Mitera, Nele Berghmans, Philippe E. Van den Steen, Christin Friedrich, Georg Gasteiger, Carine Wouters, Patrick Matthys”}]]

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In macrophage activation syndrome, a severe cytokine storm syndrome with liver inflammation, liver type 1 innate lymphoid cells (ILC1s) rapidly produce proinflammatory cytokines. However, disease progression results in liver ILC1 apoptosis. In addition, disease development was unaltered in Hobit knockout mice, which lack liver ILC1s, indicating their dispensability for disease. Abstract Macrophage activation syndrome (MAS) … Read more

Sphingosine‐1‐phosphate receptor type 4 is critically involved in the regulation of peritoneal B‐1 cell trafficking and distribution in vivo. [[{“value”:”Janik Riese, Annabel Kleinwort, Maurice Hannemann, Celine Hähnel, Stephan Kersting, Tobias Schulze”}]]

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Sphingosine-1-phosphate (S1P) is implicated in the regulation of peritoneal B-cell trafficking. Here we show that the effects of S1P on peritoneal B-1 cell migration are mediated by the receptor S1PR4 via direct chemotactic action as well as via upregulation of the expression level of chemokine receptors CXCR4 and CXCR5. Abstract B-1 cells are crucially involved … Read more

Innate immunity champions: The diverse functions of macrophages. [[{“value”:”Francesca Biscu, Anissa Zouzaf, Donatella Cicia, Clare Pridans, Gianluca Matteoli”}]]

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This review highlights the pivotal role of macrophages in regulating tissue homeostasis and immune response during disease. Advanced omics technologies reveal their adaptability within tissue-specific niches, influenced by their metabolic states. Understanding these dynamics is crucial for developing targeted therapies that modulate macrophage function, offering innovative strategies for managing chronic inflammatory conditions. Abstract Macrophages are … Read more

Reduction in mucosal‐associated invariant T cells (MAIT) in APECED patients is associated with elevated serum IFN‐γ concentration. [[{“value”:”Iivo Hetemäki, Joona Sarkkinen, Huai Hui Wong, Nelli Heikkilä, Saila Laakso, Simo Miettinen, Mikko I. Mäyränpää, Outi Mäkitie, T Petteri Arstila, Eliisa Kekäläinen”}]]

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We found a reduced frequency of circulating mucosal-associated invariant T cells (MAITs) in patients with APECED with a clear negative correlation to inflammatory markers CRP, IL-18, and IFN-γ. These findings suggest that the decrease in MAITs is secondary to type 1 immune dysregulation present in the disease. Abstract Mucosal-associated invariant T cells (MAIT) are innate-like … Read more

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