Expression level of tissue Ag determines the fate of responding T cells in vivo.
Rapa rescues the generation of peripheral Foxp3+ T cells even at a high Ag dose.
A low level of endogenous tissue Ag differentiates stable Foxp3+ T cells in vivo.
ANTIGEN RECOGNITION AND RESPONSES
Polyglutamine-Related Aggregates Can Serve as a Potent Antigen Source for Cross-Presentation by Dendritic Cells
CTL responses require overlap of directly and cross-presented peptide repertoires.
Apoptosis, but not necrosis, is associated with global protein aggregation.
Aggregation aids overlap of directly and cross-presented epitopes.
Siglec-15 on osteoclasts is crucial for bone erosion in an arthritis model.
Murine Siglec-15 is expressed almost exclusively on osteoclasts.
Human Siglec-15 is expressed broadly on myeloid cells of peripheral blood.
Adenosine-to-Inosine RNA Editing of Alu Double-Stranded (ds)RNAs Is Markedly Decreased in Multiple Sclerosis and Unedited Alu dsRNAs Are Potent Activators of Proinflammatory Transcriptional Responses
A-to-I RNA editing of Alu dsRNAs is markedly decreased in MS.
Endogenous Alu dsRNAs are potent activators of IFN and NF-κB responses.
Minor RNA editing of active Alu dsRNAs abrogates this activity.
CLINICAL AND HUMAN IMMUNOLOGY
Innate Immune Responses and Gut Microbiomes Distinguish HIV-Exposed from HIV-Unexposed Children in a Population-Specific Manner
Innate immune and stool microbiome signatures of HEU children are region specific.
Differences in HEU immune responses were unrelated to the microbiome.
Future immune studies of HEU children must be studied across diverse settings.
IFN signaling is ongoing in CLL patients treated with ibrutinib.
Ibrutinib modulates IFN-stimulated gene expression but preserves survival signaling.
Plasma-derived IgA induces death in neutrophils under inflammatory conditions.
IgA-mediated death involves PI3K-, p38 MAPK–, and JNK-dependent pathways.
Zbtb20 Restrains CD8 T Cell Immunometabolism and Restricts Memory Differentiation and Antitumor Immunity
Zbtb20 is an important regulator of effector and memory CD8 T cell immunometabolism.
Differentiation to a memory precursor phenotype is favored by Zbtb20 deficiency.
CD8 T cells deficient in Zbtb20 confer enhanced protection against tumors.
Regulatory T Cells Maintain Selective Access to IL-2 and Immune Homeostasis despite Substantially Reduced CD25 Function
Neutralization of IL-2 in vivo does not immediately disrupt Treg cell function.
Treg cells maintain normal IL-2 signaling with the CD25 Ab PC61 in vivo.
IMMUNE SYSTEM DEVELOPMENT
Stage 3 and 4A but not 4B NKDIs retain non–NK ILC developmental potential.
Notch activation in the presence of stroma promotes ILC2 and ILC3 differentiation.
NOTCH1 and NOTCH2 regulate ILC differentiation from stage 3 and 4A cells.
Macrophages are “whistle blowers” to initiate emergency myelopoiesis in zebrafish.
The IL-1b–NF-κB&C/ebpβ axis is crucially involved in the emergency myelopoiesis.
IMMUNOTHERAPY AND VACCINES
Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells
P. pentosaceus MVs possess potent anti-inflammatory immunotherapeutic potential.
P. pentosaceus MVs upregulate IL-10, Arg-1, and PD-L1 levels on myeloid cells.
MVs promote M2-like macrophage and MDSC differentiation.
INFECTIOUS DISEASE AND HOST RESPONSE
A substantial number of recovered subjects (20%) have no or low titers of NAbs.
Recovery from infection does not seem solely dependent on high NAb titers.
NAb titers are correlated well with severity of disease and age of the affected.
Role of Tunneling Nanotube–like Structures during the Early Events of HIV Infection: Novel Features of Tissue Compartmentalization and Mechanism of HIV Spread
HIV seeding occurs early in different tissues and anatomical sites.
HIV tissue spread is cell type–, tissue-, and ART-dependent.
HIV uses tunneling nanotube–like structures to infect neighboring cells.
The Presence of Antibody-Dependent Cell Cytotoxicity–Mediating Antibodies in Kaposi Sarcoma–Associated Herpesvirus–Seropositive Individuals Does Not Correlate with Disease Pathogenesis or Progression
KSHV Abs mediate ADCC responses against lytically reactivated cells.
Over one-third of KSHV-seropositive individuals have ADCC responses.
ADCC does not differ between KS patients and asymptomatic controls.
Airway Macrophages Mediate Mucosal Vaccine–Induced Trained Innate Immunity against Mycobacterium tuberculosis in Early Stages of Infection
Mucosal TB vaccine induces memory AwMs.
Vaccine-trained AwMs enhance anti-TB innate immunity.
Macrophage-mediated anti-TB innate immunity is independent of T cells and monocytes.
The Immune System Fails to Mount a Protective Response to Gram-Positive or Gram-Negative Bacterial Prostatitis
UPEC and E. faecalis have a tropism for the mouse prostate over the bladder.
There is no protective immune memory to a second bacterial prostate infection.
Bacterial uptake is altered in challenge infection compared with primary.
INNATE IMMUNITY AND INFLAMMATION
RIPK3 promotes pyrin inflammasome activation independent of its role in necroptosis.
RIPK3 modulates the mTOR pathway to regulate pyrin inflammasome activation.
Inhibition of mTOR promotes Mefv expression and pyrin inflammasome activation.
Non–Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice
BP180 is expressed in bone marrow mesenchymal stem cells.
BP180 in bone marrow mesenchymal stem cells regulates granulopoiesis.
Mitochondrial Reactive Oxygen Species Participate in Signaling Triggered by Heme in Macrophages and upon Hemolysis
Activation of TLR4 by heme or LPS triggers distinct signaling outcomes.
Heme signals via TLR4, Syk, and ROS to induce cytokine expression in macrophages.
Death due to hemolysis in mice depends on TLR4, TNFR1, and mitochondrial ROS.
An Allosteric Shift in CD11c Affinity Activates a Proatherogenic State in Arrested Intermediate Monocytes
iMo recruitment via CD11c and VLA-4 binding VCAM-1 is enhanced in cardiac patients.
CD11c mechanosignals phenotypic conversion of iMo to an inflammatory state.
ADAM17 on iMo cleaves membrane CD16, marking inflammatory gene activation.
Inflammation Unrestrained by SIRPα Induces Secondary Hemophagocytic Lymphohistiocytosis Independent of IFN-γ
SIRPα deficiency enables various inflammatory stimuli to confer sHLH/CSS in mice.
Macrophage depletion, but not IFN-γ neutralization, precludes sHLH in SIRPα−/− mice.
SIRPα negatively regulates TLR9 signaling by inhibiting Erk1/2 and p38 activation.
Absence of the C5a Receptor C5aR2 Worsens Ischemic Tissue Injury by Increasing C5aR1-Mediated Neutrophil Infiltration
C5aR2 is protective in gut ischemia-reperfusion injury.
C5aR2 negatively regulates C5aR1-induced neutrophil infiltration.
C5aR2 promotes neutrophil mobilization/egress from bone marrow.
Adrenic acid is the first omega-6 fatty acid with proresolving functions.
Adrenic acid inhibits leukotriene B4 production, specifically in neutrophils.
Adrenic acid treatment alleviates leukotriene B4–mediated experimental arthritis.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
IgG1 Abs with different V regions bind to FcRn with different affinity.
The V region of IgG1 dictates the mechanism of molecular recognition by FcRn.
Formation of immune complexes modifies the mechanism of IgG binding to FcRn.
Peptide Binding to HLA-E Molecules in Humans, Nonhuman Primates, and Mice Reveals Unique Binding Peptides but Remarkably Conserved Anchor Residues
HLA-E*01:01, HLA-E*01:03, Mamu-E, and Qa-1b have unique motifs.
Each MHC-E molecule binds alternative peptides with conserved main anchor residues.
Nonanchor residues can play an important role in peptide binding to MHC-E.
The GM-CSF Released by Airway Epithelial Cells Orchestrates the Mucosal Adjuvant Activity of Flagellin
Flagellin induces GM-CSF production by AECs.
GM-CSF transactivates lung conventional dendritic cells.
GM-CSF drives the mucosal adjuvant activity of flagellin/TLR5.
MARCH E3 ubiquitin ligases regulate responses to anti-tumor Abs.
The tumor’s MARCH protein repertoire may determine sensitivity to those Abs.
Intratumoral Activation of 41BB Costimulatory Signals Enhances CD8 T Cell Expansion and Modulates Tumor-Infiltrating Myeloid Cells
Intratumoral 41BB agonism induces tumor regression in mouse models.
41BB agonism potentiates myeloid-mediated costimulation in tumors.
Activation of 41BBL but not 41BB in human APCs promotes costimulatory responses.
An MSS CRC patient responded rapidly to fruquintinib plus anti–PD-1 therapy.
Fruquintinib plus anti–PD-1 treatment significantly inhibited tumor growth in mice.
Fruquintinib plus anti–PD-1 treatment led to an antitumor tumor microenvironment.
Mouse 4T1 Breast Cancer Cell–Derived Exosomes Induce Proinflammatory Cytokine Production in Macrophages via miR-183
Tumor exosome–derived miR-183 regulates macrophage cytokine production.
miR-183 contributes to metastatic spread of breast tumors in vivo.
TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1/TH17 Cell Response
Myo9b deficiency in tumor cells and host mice both suppress the development of MPE.
TSAd expression mediated by Myo9b associates with TH1/TH17 cell differentiation.
Myo9b mediates MPE suppression by TSAd-dependent TH1/TH17 cell response regulation.
On the cover: Immunohistochemical staining was performed to evaluate Myo9b expression in pleural metastatic tissue sections with anti-Myo9b mAbs. Lung cancer patients with malignant pleural effusion had higher Myo9b expression levels in pleural metastatic tissues than in primary lung cancer tissues or the adjacent normal tissues. Yi, F.-S., X. Zhang, K. Zhai, Z.-Y. Huang, X.-Z. Wu, M.-T. Wu, X.-Y. Shi, X.-B. Pei, S.-F. Dong, W. Wang, Y. Yang, J. Du, Z.-T. Luo, and H.-Z. Shi. 2020. TSAd plays a major role in Myo9b-mediated suppression of malignant pleural effusion by regulating TH1/TH17 cell response. J. Immunol. 205: 2926–2935.
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