Excessive negative regulation of type I interferon disrupts viral control in individuals with Down syndrome
Individuals with Down syndrome have fewer viral infections, but when infected, they suffer from more severe disease. Malle et al. find that triplication of IFNAR1 and IFNAR2, the receptor subunits of the potent antiviral cytokine IFN-I, in DS results in hyperactive IFN-I signaling. The ensuing hyperinduction of IFNAR negative regulators suppresses subsequent IFN-I stimuli and effectively represses further antiviral defen ses. (Source: Immunity)
Source: Immunity - October 14, 2022 Category: Allergy & Immunology Authors: Louise Malle, Marta Martin-Fernandez, Sofija Buta, Ashley Richardson, Douglas Bush, Dusan Bogunovic Tags: Article Source Type: research
Transcription factor ROR α enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element
The transcription factor ROR α is recognized for contributing to Th17 cell differentiation and pathogenesis, but the underlying mechanisms are unclear. Hall, Pokrovskii, et al. find that RORα reinforces the RORγt transcriptional program by binding to a cis-regulatory element within the Rorc locus that maintains RORγt expre ssion in vivo, thus potentiating inflammatory disease. (Source: Immunity)
Source: Immunity - October 14, 2022 Category: Allergy & Immunology Authors: Jason A. Hall, Maria Pokrovskii, Lina Kroehling, Bo-Ram Kim, Seung Yong Kim, Lin Wu, June-Yong Lee, Dan R. Littman Tags: Article Source Type: research
Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation
De Vlaminck et al. examine the fate of microglia, border-associated macrophages, and recruited macrophages upon Trypanosoma brucei infection and resolution of neuroinflammation. They show how different types of brain macrophages orchestrate the immune response to invading parasites, revealing that brain-resident and recruited macrophages exhibit diverging responses and dynamics during infection and the return to homeostasis. (Source: Immunity)
Source: Immunity - October 12, 2022 Category: Allergy & Immunology Authors: Karen De Vlaminck, Hannah Van Hove, Daliya Kancheva, Isabelle Scheyltjens, Ana Rita Pombo Antunes, Jonathan Bastos, Monica Vara-Perez, Leen Ali, Myrthe Mampay, Lauren Deneyer, Juliana Fabiani Miranda, Ruiyao Cai, Luc Bouwens, Dimitri De Bundel, Guy Caljon Tags: Article Source Type: research
Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors
Broadly neutralizing antibodies (bnAbs) to the HIV envelope V2-apex are important leads for vaccine design but pose major challenges for precursor priming due to long heavy-chain complementarity-determining region 3 (HCDR3). We prioritize two V2-apex bnAbs, PCT64 and PG9, design and characterize ApexGT trimers that bind bnAb precursors, and develop membrane-bound trimers for mRNA delivery as candidate priming immunogens. (Source: Immunity)
Source: Immunity - September 29, 2022 Category: Allergy & Immunology Authors: Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Tags: Article Source Type: research
Membrane-bound mRNA immunogens lower the threshold to activate HIV Env V2 apex-directed broadly neutralizing B cell precursors in humanized mice
Eliciting broadly neutralizing antibodies (bnAbs) to HIV, such as the V2-Apex-targeted bnAb PCT64, is the goal of germline-targeting (GT) vaccines. Using humanized Ig knockin mouse models, Melzi et al. demonstrate the activation of rare PCT64 precursors with a high-affinity immunogen, ApexGT5. Furthermore, they find that mRNA-LNP-encoding membrane-bound ApexGT5 trimers lowers the affinity threshold for activation relative to protein immunogens. (Source: Immunity)
Source: Immunity - September 29, 2022 Category: Allergy & Immunology Authors: Eleonora Melzi, Jordan R. Willis, Krystal M. Ma, Ying-Cing Lin, Sven Kratochvil, Zachary T. Berndsen, Elise A. Landais, Oleksandr Kalyuzhniy, Usha Nair, John Warner, Jon M. Steichen, Anton Kalyuzhniy, Amber Le, Simone Pecetta, Manfredo Perez, Kathrin Kirs Tags: Article Source Type: research
High-throughput T cell receptor engineering by functional screening identifies candidates with enhanced potency and specificity
Vazquez-Lombardi et al. developed a high-throughput method combining mammalian display, CRISPR-targeted mutagenesis, functional screening, and deep sequencing for the engineering of T cell receptors (TCR-Engine). They applied TCR-Engine to identify potent and specific therapeutic candidates against MAGE-A3, an attra ctive cancer target for TCR immunotherapy previously complicated by off-target activity. (Source: Immunity)
Source: Immunity - September 28, 2022 Category: Allergy & Immunology Authors: Rodrigo Vazquez-Lombardi, Johanna S. Jung, Fabrice S. Schlatter, Anna Mei, Natalia Rodrigues Mantuano, Florian Bieberich, Kai-Lin Hong, Jakub Kucharczyk, Edo Kapetanovic, Erik Aznauryan, C édric R. Weber, Alfred Zippelius, Heinz Läubli, Sai T. Reddy Tags: Resource Source Type: research
Mucosal plasma cells are required to protect the upper airway and brain from infection
Whether circulating antibodies protect the nasal airway from infection is unclear. Wellford et al. show that the olfactory mucosa exists outside the reach of serum antibody due to the presence of a blood-olfactory barrier. Instead, mucosal plasma cells can be recruited to protect the upper airway and brain from infection. (Source: Immunity)
Source: Immunity - September 21, 2022 Category: Allergy & Immunology Authors: Sebastian A. Wellford, Annie Park Moseman, Kianna Dao, Katherine E. Wright, Allison Chen, Jona E. Plevin, Tzu-Chieh Liao, Naren Mehta, E. Ashley Moseman Tags: Article Source Type: research
Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting
Immune memory in humans has been shown to extend well beyond decades. Chappert et al. provide an extensive functional characterization of human splenic smallpox/vaccinia protein B5-specific MBCs, generated more than four decades ago, to decipher the distinct selection and survival mechanisms associated with MBCs longevity. (Source: Immunity)
Source: Immunity - September 20, 2022 Category: Allergy & Immunology Authors: Pascal Chappert, Fran çois Huetz, Marie-Alix Espinasse, Fabrice Chatonnet, Louise Pannetier, Lucie Da Silva, Clara Goetz, Jérome Mégret, Aurélien Sokal, Etienne Crickx, Ivan Nemazanyy, Vincent Jung, Chiara Guerrera, Sébastien Storck, Matthieu Mahéva Tags: Article Source Type: research
The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn ’s disease
The functional basis of tolerance to the gut microbiome is incompletely understood. Pedersen et al. develop an antigen-discovery approach to assess microbiota-directed T cell immunity in health and inflammation. They reveal the dynamic nature of T cell-mediated responses toward commensal Bacteroidales, highlighting inflammation-associated changes in Crohn’s disease. (Source: Immunity)
Source: Immunity - September 16, 2022 Category: Allergy & Immunology Authors: Thomas K. Pedersen, Eric M. Brown, Damian R. Plichta, Joachim Johansen, Shaina W. Twardus, Toni M. Delorey, Helena Lau, Hera Vlamakis, James J. Moon, Ramnik J. Xavier, Daniel B. Graham Tags: Article Source Type: research
A self-sustaining layer of early-life-origin B cells drives steady-state IgA responses in the adult gut
Vergani et al. use time-stamping to examine the relationship between developmental origin and the composition of the adult B cell pool. They find that B cells arising early in life substantially contribute to the IgM and IgA repertoires in unimmunized adult mice. These early-life-origin B cells form a networ k of self-sustaining IgA memory compartments that archive unique specificities not generated later in life. (Source: Immunity)
Source: Immunity - September 16, 2022 Category: Allergy & Immunology Authors: Stefano Vergani, Konjit Getachew Muleta, Cl ément Da Silva, Alexander Doyle, Trine Ahn Kristiansen, Selene Sodini, Niklas Krausse, Giorgia Montano, Knut Kotarsky, Joy Nakawesi, Hugo Åkerstrand, Stijn Vanhee, Sneh Lata Gupta, David Bryder, William Winsto Tags: Article Source Type: research
Lineage tracing reveals B cell antibody class switching is stochastic, cell-autonomous, and tuneable
During immune responses, B cells generate functionally diverse secreted antibodies through cellular differentiation and class switch recombination. Horton et al. reveal that distinct clonal mechanisms regulate alternative B cell fate decisions. For class switching, the intersection of two cell-autonomous stochastic events is required. A mathematical model utilizing molecular information and rules of change predicts complex class switch patterning durin g cell division. (Source: Immunity)
Source: Immunity - September 14, 2022 Category: Allergy & Immunology Authors: Miles B. Horton, HoChan Cheon, Ken R. Duffy, Daniel Brown, Shalin H. Naik, Carolina Alvarado, Joanna R. Groom, Susanne Heinzel, Philip D. Hodgkin Tags: Article Source Type: research
SARS-CoV-2 in immunocompromised individuals
Vardhana and colleagues discuss how discrete immunological defects in individuals with cancer and other immunosuppressive conditions have informed our understanding of the role of the immune system in protection and toxicity from SARS-CoV-2. They discuss how these immune defects affect the protective impact of vaccination strategies in these individuals and provide insight to limit COVID-19-associated morbidity in this high-risk population. (Source: Immunity)
Source: Immunity - September 12, 2022 Category: Allergy & Immunology Authors: Susan DeWolf, Justin C. Laracy, Miguel-Angel Perales, Mini Kamboj, Marcel R.M. van den Brink, Santosha Vardhana Tags: Review Source Type: research
ABCC1 transporter exports the immunostimulatory cyclic dinucleotide cGAMP
Cyclic GMP-AMP (cGAMP) is an “immunotransmitter” that can be imported into cells to activate antiviral responses, but how cGAMP exits cells is currently unknown. Maltbaek et al. identify ABCC1 as an active cGAMP exporter that modulates STING-dependent immunity. (Source: Immunity)
Source: Immunity - September 6, 2022 Category: Allergy & Immunology Authors: Joanna H. Maltbaek, Stephanie Cambier, Jessica M. Snyder, Daniel B. Stetson Tags: Article Source Type: research
Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling
IL23R is a major susceptibility gene in human autoimmune diseases, but how it confers pathogenicity to T helper cells has not been fully elucidated. Pawlak, DeTomaso et al. demonstrate that Th1-like cells require IL-23R signaling to induce colitis. These findings indicate that IL-23R functions in non-Th17 cells to drive pathogenesis during intestinal autoimmunity. (Source: Immunity)
Source: Immunity - September 6, 2022 Category: Allergy & Immunology Authors: Mathias Pawlak, David DeTomaso, Alexandra Schnell, Gerd Meyer zu Horste, Youjin Lee, Jackson Nyman, Danielle Dionne, Brianna M.L. Regan, Vasundhara Singh, Toni Delorey, Markus A. Schramm, Chao Wang, Antonia Wallrapp, Patrick R. Burkett, Samantha J. Riesen Tags: Article Source Type: research
Innate type 2 immunity controls hair follicle commensalism by Demodex mites
Type 2 cytokines are well recognized for their role in mediating allergic pathologies in skin, but their role in normal skin physiology is unclear. Ricardo-Gonzalez et al. reveal that type 2 immunity restrains skin inflammation in response to injury that is necessary to control hair follicle commensalism by Demodex mites. (Source: Immunity)
Source: Immunity - August 30, 2022 Category: Allergy & Immunology Authors: Roberto R. Ricardo-Gonzalez, Maya E. Kotas, Claire E. O ’Leary, Katelyn Singh, William Damsky, Chang Liao, Elizabeth Arouge, Iliana Tenvooren, Diana M. Marquez, Andrew W. Schroeder, Jarish N. Cohen, Marlys S. Fassett, Jinwoo Lee, Scott G. Daniel, Kyle B Tags: Article Source Type: research
