Cutting Edge: Lung-Resident T Cells Elicited by SARS-CoV-2 Do Not Mediate Protection against Secondary Infection
SARS-CoV-2 infection elicits pulmonary resident CD4+ and CD8+ T cells.
Pulmonary T cells are not sufficient for protection against secondary SARS-CoV-2.
Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer–BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines
BNT162b2 induces release of exosomes carrying SARS-CoV-2 spike protein.
Abs to SARS-CoV-2 develop after detection of circulatory exosomes.
Exosomes with SARS-CoV-2 spike protein are immunogenic in mice.
Cutting Edge: Caspase-8 Is a Linchpin in Caspase-3 and Gasdermin D Activation to Control Cell Death, Cytokine Release, and Host Defense during Influenza A Virus Infection
Caspase-8 autoprocessing restricts gasdermin D–mediated pyroptosis and cytokine release.
Caspase-8–mediated caspase-3 activation leads to its anti-inflammatory effects.
Uncleavable caspase-8 promotes host defense during influenza A virus infection.
Cutting Edge: DOCK8 Regulates a Subset of Dendritic Cells That Is Critical for the Development of Experimental Autoimmune Encephalomyelitis
Deficiency of DOCK8 in dendritic cells limits the development of EAE.
DOCK8 controls the presence of cDC2 in the spleen and migratory DC in the lymph nodes.
Migratory DC prime myelin-specific CD4+ T cells.
CLINICAL AND HUMAN IMMUNOLOGY
STAT3 Gain-of-Function Mutations Underlie Deficiency in Human Nonclassical CD16+ Monocytes and CD141+ Dendritic Cells
STAT3 gain-of-function causes a novel disorder of dendritic cells and monocytes.
STAT3 gain-of-function patients lack nonclassical monocytes and certain dendritic cells.
STAT3 mutations cause altered dendritic cell differentiation.
cffDNA induces innate inflammatory responses in maternal monocytes.
This response activates T and endothelial cells and causes myometrial contraction.
cffDNA may have an important role in the initiation of parturition.
Maternal and Infant Immune Repertoire Sequencing Analysis Identifies Distinct Ig and TCR Development in Term and Preterm Infants
Maternal–fetal immune repertoire analyses provide insights to preterm labor.
Clonal convergence suggests a response to shared stimuli.
Lactoferrin Potentiates Inducible Regulatory T Cell Differentiation through TGF-β Receptor III Binding and Activation of Membrane-Bound TGF-β
Lactoferrin induces Foxp3+ Tregs via TβRIII→ROS→mTGF-β activation→Smad3 signaling.
Suppression by these Tregs exerts through CD39/CD73-mediated adenosine generation.
Peroral administration of lactoferrin alleviates DSS-induced colitis.
The Role of Properdin in C5 Convertase Activity and C5b-9 Formation in the Complement Alternative Pathway
Properdin is required for AP-mediated C5 convertase activity and C5b-9 formation.
Properdin induces a switch in convertase specificity toward C5.
Properdin has a crucial role in AP activation and total complement activation.
CD28 is a costimulatory receptor expressed by porcine T cells.
Superagonistic anti-CD28 mAbs elicit a human-like response in porcine T cells.
IL-15 trans-presentation (TP) and Ag presentation rely on APC–T cell interaction.
We showed IL-15R subunit assembly upon TP and joint motion with MHC to the IS.
IL-15R and TCR do not amplify each other’s signaling; TP is self-sufficient.
The Presence of Activated T Cell Subsets prior to Transplantation Is Associated with Increased Rejection Risk in Pancreas Transplant Recipients
Activated gut-homing CD4+ and CD8+ T cells are associated with PTx rejection.
Tregs are activated in rejectors, but produce less IL-10.
Post-PTx conditioning affects CD4+ and CD8+ T cell number and functionality.
Retroposition of the Long Transcript from Multiexon IFN-β Homologs in Ancestry Vertebrate Gave Rise to the Proximal Transcription Elements of Intronless IFN-β Promoter in Humans
Long and short transcripts were transcribed from African clawed frog IFN1, as IFNφ1 in zebrafish.
The long transcript contains PRD-like sites and TATA box in its proximal promoter.
Transcriptional conservation in IFN-β homologs may be resulted from retroposition.
IMMUNOTHERAPY AND VACCINES
Selective Inhibition of the Interaction between SARS-CoV-2 Spike S1 and ACE2 by SPIDAR Peptide Induces Anti-Inflammatory Therapeutic Responses
We have engineered the spike S1–interacting domain of ACE2 receptor (SPIDAR) peptide.
The wtSPIDAR, not mSPIDAR, inhibits SARS-CoV-2 spike S1–induced inflammation.
Intranasal wtSPIDAR, not mSPIDAR, protects mice from SARS-CoV-2 spike S1 toxicity.
INNATE IMMUNITY AND INFLAMMATION
Human Cytomegalovirus Infection Promotes Expansion of a Functionally Superior Cytoplasmic CD3+ NK Cell Subset with a Bcl11b-Regulated T Cell Signature
HCMV infection promotes expression of canonical T cell molecules in NK cells.
CD3-positive NK cells are functionally superior in ADCC response.
Point mutation of L-PGDS cysteine 65 decreases PGD2 production in vivo.
L-PGDS attenuates pulmonary edema formation via PGD2-dependent way.
L-PGDS reduces leukocyte infiltration and mucin production via a PGD2-independent way.
The Trypanosome-Derived Metabolite Indole-3-Pyruvate Inhibits Prostaglandin Production in Macrophages by Targeting COX2
The Trypanosoma brucei–derived metabolite I3P blocks PG production in macrophages.
I3P directly inhibits COX2 enzymatic activity.
I3P boosts COX2 expression through AhR activation and a PG feedback loop.
4-Octyl-Itaconate and Dimethyl Fumarate Inhibit COX2 Expression and Prostaglandin Production in Macrophages
4-OI reduces COX2 expression and inhibits PG production in macrophages.
DMF also attenuates COX2 expression in macrophages and decreases PGs.
The 4-OI– and DMF-induced decrease in COX2 and PGs is NRF2 independent.
Zebrafish prmt2 attenuates antiviral innate immunity.
Prmt2 catalyzes arginine methylation of traf6 at R100.
Prmt2 prevents K63-linked autoubiquitination of traf6.
Pre-existing SARS-CoV-2–reactive B cells are found in tonsillar tissue.
SARS-CoV-2–reactive Abs can be generated de novo.
Pre-existing SARS-CoV-2–reactive Abs have neutralizing potential.
Pre-existing atopy protects against paramyxovirus-induced airway disease.
Neutrophils and IL-4 are critical for protection against postviral airway disease.
Anti–PD-1 promotes the function of Tregs in a claudin-low model of breast cancer.
PD-1 blockade increases proliferation, survival, and suppressive function of Tregs.
NOVEL IMMUNOLOGICAL METHODS
Development of Neutralizing Multimeric Nanobody Constructs Directed against IL-13: From Immunization to Lead Optimization
Anti–IL-13 nanobodies can be generated using a standard immunization protocol.
Nanobodies can be easily engineered in a multimeric format.
Mutiparatopic nanobodies allow better inhibition than multivalent ones.
On the cover: Heatmap of chromatin accessibility of classical NK cells (left) and human CMV (HCMV)-induced NK cells (right), demonstrating that HCMV-induced NK cells have increased chromatin accessibility in genes associated with the biological processes involved in TCR signaling, NK cell cytotoxicity, cytokine signaling, and leukocyte activation. Wu, Z., C. M. Lau, R. Sottile, J.-B. Le Luduec, M. K. Panjwani, P. M. Conaty, K. Srpan, K. L. Sampaio, T. Mertens, S. P. Adler, A. B. Hill, J. N. Barker, N.-K. V. Cheung, J. C. Sun, and K. C. Hsu. 2021. Human cytomegalovirus infection promotes expansion of a functionally superior cytoplasmic CD3+ NK cell subset with a Bcl11b-regulated T cell signature. J. Immunol. 207: 2534–2544.
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