ALLERGY AND OTHER HYPERSENSITIVITIES
Activation of P2Y11R on LAD2 human mast cells enhances allergic degranulation.
The enhancement does not require intracellular Ca2+ mobilization.
P2Y11R enhancement of degranulation involves PI3K(δ) and Akt, but not PDK-1.
ANTIGEN RECOGNITION AND RESPONSES
Synthetic Peptides with Inadvertent Chemical Modifications Can Activate Potentially Autoreactive T Cells
Chemical modifications can alter the immunogenicity of synthetic peptides.
TCR degeneracy can extend to ligand structures that are not known to occur in nature.
Chemically modified synthetic peptides can activate potentially autoreactive T cells.
CD22 Controls Germinal Center B Cell Receptor Signaling, Which Influences Plasma Cell and Memory B Cell Output
CD22−/− germinal center B cells have a competitive disadvantage.
CD22 inhibits BCR signaling on germinal center B cells.
BCR signaling on CD22−/− germinal center B cells induces apoptosis.
CLINICAL AND HUMAN IMMUNOLOGY
Activation and Kinetics of Circulating T Follicular Helper Cells, Specific Plasmablast Response, and Development of Neutralizing Antibodies following Yellow Fever Virus Vaccination
Increased germinal center activity was observed 1 wk following YFV vaccination.
YFV-specific plasmablasts expanded and peaked 2 wk following vaccination.
Study subjects developed neutralizing Abs and YFV-specific memory B cells.
Epigenetic Analysis of the Chromatin Landscape Identifies a Repertoire of Murine Eosinophil-Specific PU.1-Bound Enhancers
Active (H3K27ac+) eosinophil–specific enhancers are enriched for PU.1.
Active eosinophil–specific enhancers are enriched in key functional gene pathways.
Eosinophil superenhancers associate with genes with risk loci for allergic disease.
IMMUNE SYSTEM DEVELOPMENT
NR4A3 has unique, nonredundant roles in T cell development.
Nr4a3−/− mice accumulate Tregs and CD8+ thymocytes with an activated phenotype.
NR4A3 limits autoimmunity.
INFECTIOUS DISEASE AND HOST RESPONSE
Mycobacterium bovis Bacillus Calmette–Guérin–Infected Dendritic Cells Induce TNF-α–Dependent Cell Cluster Formation That Promotes Bacterial Dissemination through an In Vitro Model of the Blood–Brain Barrier
BCG-infected DCs form cellular clusters with PBMCs, promoting local dissemination.
Clusters on brain endothelial cells induce inflammation and barrier integrity loss.
TNF-α inhibition reduces cluster formation and mitigates endothelial damage.
IL-6 Generated from Human Hematopoietic Stem and Progenitor Cells through TLR4 Signaling Promotes Emergency Granulopoiesis by Regulating Transcription Factor Expression
TLR4 expressed on HSPCs is involved in the induction of emergency granulopoiesis.
IL-6 produced via TLR4 signaling promotes emergency granulopoiesis.
IL-6 regulates the expression of transcription factors to promote granulopoiesis.
IFN-γ Manipulates NOD1-Mediated Interaction of Autophagy and Edwardsiella piscicida to Augment Intracellular Clearance in Fish
NOD1 mediates the cross-talk between autophagy and E. piscicida in fish.
Autophagy is a critical defense pathway against intracellular bacteria in fish.
The Quality of SARS-CoV-2–Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated
Coinhibitory receptors are associated with activated T cells in COVID-19.
Our results refute the concept of T cell exhaustion in COVID-19 patients.
Th2 phenotype was associated with milder whereas a robust Th17 with severe disease.
INNATE IMMUNITY AND INFLAMMATION
Host Defense against Klebsiella pneumoniae Pneumonia Is Augmented by Lung-Derived Mesenchymal Stem Cells
A homogeneous population of LMSCs is purified from mouse lungs using Sca-1.
LMSCs modulate neutrophil and macrophage functions and show bacterial killing.
LMSCs improve survival, minimize inflammation, and enhance bacterial clearance.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Tyr192 in Lck kinase participates in the regulation of other Lck phosphosites.
Tyr192 contributes to Lck SH2 domain binding.
Lck mutated on both Y192E and Y505F unlocks its enzymatic potential.
Structure-based algorithms for Strep A vaccine design are presented.
Structure and sequence similarity of M peptides and cross-reactivity of M Abs are described.
The number of M peptides to construct a potentially broadly protective Strep A vaccine is shown.
Pathway-Specific Defects in T, B, and NK Cells and Age-Dependent Development of High IgE in Mice Heterozygous for a CADINS-Associated Dominant Negative CARD11 Allele
CARD11R30W/+ mice exhibit pathway-specific defects in T, B, and NK cells.
CARD11R30W/+ mice develop high IgE in an age-dependent manner with 50% penetrance.
High IgE in CARD11R30W/+ mice is uncoupled from Th2 expansion and atopic dermatitis.
Postnatal Ozone Exposure Disrupts Alveolar Development, Exaggerates Mucoinflammatory Responses, and Suppresses Bacterial Clearance in Developing Scnn1b-Tg+ Mice Lungs
Ozone induces alveolar space remodeling in the developing lungs.
Ozone promotes type 2 mucoinflammation in the developing lungs.
Ozone worsens mucoinflammatory responses in ongoing CF-like lung disease.
Expansion of Unique Hepatitis C Virus–Specific Public CD8+ T Cell Clonotypes during Acute Infection and Reinfection
Thirteen unique public clonotypes specific for the HCV NS3-1073 epitope are identified.
Public clonotypes expanded during acute HCV infection and reinfection.
Low frequency of cross-reactive TCRs targeting other HLA-A2–restricted epitopes is evident.
Stimulated bone marrow–derived dendritic cells lyse T lymphoma target cells in vitro.
Dendritic cell–mediated cytotoxicity is dependent on peroxynitrite.
Dendritic cell transfers into T lymphoma-bearing mice show antitumor efficacy.
Fractalkine Elicits Chemotactic, Phenotypic, and Functional Effects on CX3CR1+CD27− NK Cells in Obesity-Associated Cancer
Intratumoral NK cell frequencies decline as visceral obesity increases in EAC.
CX3CR1 antagonism has potential to spare NK cells from depletion in EAC omentum.
Fractalkine promotes cytokine production and a CX3CR1−CD27+ phenotype in NK cells.
NOVEL IMMUNOLOGICAL METHODS
Deciphering the Interaction between Neonatal Fc Receptor and Antibodies Using a Homogeneous Bioluminescent Immunoassay
A NanoBiT homogeneous immunoassay to analyze IgG/FcRn interactions is described.
Affinities of eight Abs to hFcRn, cFcRn, mFcRn, and rFcRn were determined.
NanoBiT homogeneous immunoassays are rapid, easy to perform, and reproducible.
On the cover: Mycobacterium-infected dendritic cell-induced cluster formation on brain endothelial cells leads to cluster associated damage in an in vitro blood-brain barrier model. Bacillus Calmette-Guérin–infected (white) CD11c-eYFP dendritic cells (green) recruit PBMCs (blue, in cluster) to the site of infection forming clusters that cause local inflammation (ICAM staining, red) leading to decreased barrier properties. Gilpin, T. E., F. R. Walter, M. Herbath, M. Sandor, and Z. Fabry. 2021. Mycobacterium bovis bacillus Calmette–Guérin–infected dendritic cells induce TNF-α–dependent cell cluster formation that promotes bacterial dissemination through an in vitro model of the blood–brain barrier. J. Immunol. 207: 1065–1077.
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