Cutting Edge: ST8Sia6-Generated α-2,8-Disialic Acids Mitigate Hyperglycemia in Multiple Low-Dose Streptozotocin–Induced Diabetes
Siglec-E is expressed on IRMs.
In vivo, ST8Sia6 generates ligands for Siglec-E.
Overexpression of ST8Sia6 preserves β cells upon diabetes induction.
ALLERGY AND OTHER HYPERSENSITIVITIES
Extracellular ATP Augments Antigen-Induced Murine Mast Cell Degranulation and Allergic Responses via P2X4 Receptor Activation
Ag-induced MC degranulation is enhanced by P2X4 receptor activation.
P2X4 receptor activation augments Ag-induced Syk phosphorylation.
Passive anaphylaxis responses are reduced in P2X4 receptor–deficient mice.
Group 2 Innate Lymphoid Cells Promote Development of T Follicular Helper Cells and Initiate Allergic Sensitization to Peanuts
IL-13 is indispensable for the production of IgE Abs to peanuts.
Subsets of lung ILC2s produce IL-13 upon airborne exposure to peanut flour.
Mice deficient in ILC2s produce lower titers of peanut-specific IgE Abs.
Secreted Phospholipase A2 Group X Acts as an Adjuvant for Type 2 Inflammation, Leading to an Allergen-Specific Immune Response in the Lung
sPLA2-X serves as an effective adjuvant for a T2 immune response in the lungs.
The adaptive immune response requires the enzymatic activity of sPLA2-X.
The innate immune response is not fully dependent upon sPLA2-X enzymatic activity.
ANTIGEN RECOGNITION AND RESPONSES
The Impact of MHC Class I Dose on Development and Maintenance of the Polyclonal Naive CD8+ T Cell Repertoire
Hemizygous MHCI expression impacts CD8+ T cell maintenance but not generation.
MHCI hemizygous mice show selective retention of high-quality T cells.
CD8+ T cells from hemizygous mice are functionally superior after virus infection.
Blockade of BAFF Reshapes the Hepatic B Cell Receptor Repertoire and Attenuates Autoantibody Production in Cholestatic Liver Disease
A focused hepatic BCR repertoire is generated during cholestatic liver disease.
Blockade of BAFF reshapes BCR repertoire and reduces autoantibody production.
Depletion of B cells reduces both the hepatic fibrosis and autoantibody production.
Costimulation Blockade Disrupts CD4+ T Cell Memory Pathways and Uncouples Their Link to Decline in β-Cell Function in Type 1 Diabetes
Costimulation blockade reduces the loss of β-cell function in type 1 diabetes.
CB affects peripheral regulatory and conventional CD4+ but not CD8+ T cell subsets.
CB blunts relationship between disease progression and CD4+ memory T cell subsets.
CLINICAL AND HUMAN IMMUNOLOGY
Thymic-derived Tregs are the most attractive cell type for adoptive cell therapy.
Tregs that express the surface marker GPA33 can stably be expanded with high purity.
Developing Tregs become GPA33+ around thymic exit, but TGF-β–induced Tregs are GPA33−.
Term pregnancy dNK generate distinct cytolytic responses to K562, PMA/I, and HCMV.
Unlike first trimester dNK, term pregnancy dNK are not skewed to recognize HLA-C.
Protein and mRNA profiles suggest term pregnancy dNK are a distinct type of NK cell.
Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR-21–Peli1–c-Rel Pathway Prevents Autoimmunity
TH17 cells show distinct metabolic and epigenetic states in vitro and in vivo.
A miR-21–Peli1–c-Rel pathway controls glycolysis of pathogenic TH17 cells.
TGF-β and IL-15 Synergize through MAPK Pathways to Drive the Conversion of Human NK Cells to an Innate Lymphoid Cell 1–like Phenotype
TGF-β drives the conversion of human circulating NK cells to an ILC1-like phenotype.
CyTOF profiling was used to elucidate heterogeneity in the stages of conversion.
TGF-β–mediated conversion is driven by MAPK signaling and is enhanced by IL-15.
Genome-Wide DNA Methylation and RNA Analysis Reveal Potential Mechanism of Resistance to Streptococcus agalactiae in GIFT Strain of Nile Tilapia (Oreochromis niloticus)
Whole-genome bisulfite sequencing distinguishes between resistant and susceptible O. niloticus.
Promoter methylation regulates gene expression in immune-related genes.
An Alternative Splicing of Tupaia STING Modulated Anti-RNA Virus Responses by Targeting MDA5-LGP2 and IRF3
Tupaia STING has two alternative splicing isoforms, tSTING-FL and tSTING-mini.
tSTING-mini is critical for RNA virus-induced antiviral signaling transduction.
tSTING-mini enhances MDA5–LGP2-mediated antiviral response and IRF3 phosphorylation.
Intravenous Infusion of Cortisol, Adrenaline, or Noradrenaline Alters Porcine Immune Cell Numbers and Promotes Innate over Adaptive Immune Functionality
Cortisol strongly decreases porcine adaptive immune cells and increases neutrophils.
Catecholamines exert acute effects on porcine immune cell numbers and function.
All stress hormones promote innate over adaptive immune functionality in pigs.
CD4+ T cell–expressed CD83 regulates T cell responses in vitro and in vivo.
CD83+CD4+ T cells control CD40 expression and IL-12 production of DCs.
The Abundance and Availability of Cytokine Receptor IL-2Rβ (CD122) Constrain the Lymphopenia-Induced Homeostatic Proliferation of Naive CD4 T Cells
Naive CD4 T cells are impaired in lymphopenia-induced proliferation.
Limited availability of IL-2Rβ impedes homeostatic IL-15 signaling in CD4 T cells.
Forced IL-2Rβ expression permits effective LIP of naive CD4 T cells.
Xbp1s inhibits BCR tonic signaling, causing rapid death of FOB cells but not MZB cells.
Among many UPR-activated molecules, Xbp1s is the only one that causes FOB cell death.
BCR-mediated survival and clonal expansion responses are independently regulated.
IMMUNE SYSTEM DEVELOPMENT
The loss of UHRF1 impairs the commitment to αβ T cell lineage.
UHRF1 deficiency promotes development of the Tγδ17.
UHRF1 mediates the epigenetic regulation of EGR1.
Bmi1 regulates self-renewal ability of B-1a cells via Ink4-Arf and possibly Kdm5b.
Bmi1 may be involved in the developmental process of B-1 progenitors to B-1a cells.
FALCs, the niche for B-1a cells, are not altered in Bmi1−/− mice.
Distinct peptide-binding motifs for HLA-DP alleles were identified.
Binding motifs are associated with structural differences across HLA-DP molecules.
New functional hierarchies were demonstrated among HLA-DP alleles.
IMMUNOTHERAPY AND VACCINES
Select NulOs displayed on gonococcal LOS render bacteria susceptible to complement.
CMP-NulOs show promise against multidrug-resistant gonorrhea in preclinical studies.
CMP-Leg5,7Ac2 and CMP-Kdn are the current lead candidates.
CARD9-Associated Dectin-1 and Dectin-2 Are Required for Protective Immunity of a Multivalent Vaccine against Coccidioides posadasii Infection
IL-17A is critical for GCP-rCpa1 vaccine–mediated protection against Coccidioides.
GCP-rCpa1 is recognized by macrophages expressing Dectin-1 and Dectin-2.
GCP-rCpa1 activates CLR-CARD9 signaling to induce protective Th17 immunity.
INFECTIOUS DISEASE AND HOST RESPONSE
CD25-Targeted IL-2 Signals Promote Improved Outcomes of Influenza Infection and Boost Memory CD4 T Cell Formation
Treg-boosting IL-2 complexes induce inflammatory factors systemically and in lungs.
Treg-boosting IL-2 complexes reduce immunopathology following IAV infection.
Treg-boosting IL-2 complexes promote CD4 T cell fitness to survive to form memory.
An SAMT-247 Microbicide Provides Potent Protection against Intravaginal Simian Immunodeficiency Virus Infection of Rhesus Macaques, whereas an Added Vaccine Component Elicits Mixed Outcomes
SAMT-247 microbicide induces robust SIV protection in female rhesus macaques.
Strong vaccine-induced mucosal and systemic immunity did not delay SIV acquisition.
SAMT-247/vaccine combination enhanced protection compared with vaccine-only regimen.
INNATE IMMUNITY AND INFLAMMATION
IL-1R signaling is not necessary to control acute or chronic T. gondii burden.
IL-1R signaling limits cell death in liver and adipose tissue at acute infection.
IL-1R prevents recovery from acute weight loss and drives chronic cachexia.
Activation of CB1R Promotes Lipopolysaccharide-Induced IL-10 Secretion by Monocytic Myeloid-Derived Suppressive Cells and Reduces Acute Inflammation and Organ Injury
Δ9-THC increases IL-10 and reduces IL-6 and CCL2 in endotoxemic mice via CB1R.
Δ9-THC decreases lung inflammation and organ injury in endotoxemic mice.
Monocytic-MDSCs mediate Δ9-THC–induced IL-10 upregulation in endotoxemic mice.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
αβ TCRs, A11 and B12A, recognize CD155 independent of MHC presentation.
CDR3 of α- or β-chain alone is insufficient to discriminate against MHC binding.
This study reports the structure of αβ TCR in complex with a non-MHC ligand.
Cullin 3 Is Crucial for Pro-B Cell Proliferation, Interacts with CD22, and Controls CD22 Internalization on B Cells
Cullin 3 is identified as a novel CD22 interacting protein.
Cullin 3 binds to CD22 and regulates CD22 surface expression and internalization.
Cullin 3 controls pro-B cell proliferation and is important for B cell signaling.
Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination
The auxoGTU vaccine and EP triggered different components of innate immunity.
The auxoGTU vaccine with EP induces a local release of IL-15 and activation of LC.
AIM-2 seems to be a sensor of the auxoGTU vaccine.
Distinct Features of Human Myeloid Cell Cytokine Response Profiles Identify Neutrophil Activation by Cytokines as a Prognostic Feature during Tuberculosis and Cancer
Neutrophils express robust transcriptional profiles following cytokine stimulation.
Myeloid cell gene signatures can stratify patients and predict disease outcomes.
Suppression of Mll1-Complex by Stat3/Cebpβ–Induced miR-21a/21b/181b Maintains the Accumulation, Homeostasis, and Immunosuppressive Function of Polymorphonuclear Myeloid-Derived Suppressor Cells
Suppression of Wdr5/Ash2l/Ml11 promotes PMN-MDSCs’ accumulation and function.
Stat3/Cebpβ downregulate Wdr5/Ash2l/Ml11 by upregulating miR–21a/21b/181b.
Radiation fails to promote cDC1 maturation in poorly radioimmunogenic tumors.
Impaired cDC1 activation following radiation limits the response to treatment.
Adjuvants that drive cDC1 maturation improve tumor responses to radiation.
NOVEL IMMUNOLOGICAL METHODS
Correction for batch and nonspecific binding enhances Luminex data.
Our novel R utility automates these corrections.
Utility can uncover undetected biological patterns in Luminex data.
Systematic Profiling of Full-Length Ig and TCR Repertoire Diversity in Rhesus Macaque through Long Read Transcriptome Sequencing
PacBio Iso-Seq enables generation of immune repertoire C region references.
Full-length CCS reads benchmark targeted immune repertoire assay efficiencies.
On the cover: Two-dimensional t-distributed stochastic neighbor embedding plot representing mouse spleen CD4+ T cell activation at 12 h. Three conditions overlap: saline (grey), LPS + vehicle (red), and LPS + Δ9-tetrahydrocannabinol (blue). Made with FlowJo software version 10.6.1 (Becton, Dickinson and Company). Joffre, J., C.-C. Yeh, E. Wong, M. Thete, F. Xu, I. Zlatanova, E. Lloyd, L. Kobzik, M. Legrand, and J. Hellman. 2020. Activation of CB1R promotes lipopolysaccharide-induced IL-10 secretion by monocytic myeloid-derived suppressive cells and reduces acute inflammation and organ injury. J. Immunol. 204: 3339–3350.
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