Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages
Cutting Edge: Reduced Adenosine-to-Inosine Editing of Endogenous Alu RNAs in Severe COVID-19 Disease
Severe COVID-19 is associated with reduced A-to-I editing of Alu dsRNAs.
Infection of dendritic cells with COVID-19 causes reduced A-to-I editing.
Unedited, but not edited, Alu dsRNAs activate IRF and NF-κB responses.
ANTIGEN RECOGNITION AND RESPONSES
SP subunits are not upregulated in IP-deficient mice during viral infection.
IP is not required to control protein homeostasis during viral infection.
There is no evidence for proteotoxic stress in IP-deficient mice during viral infection.
Novel Potent IFN-γ–Inducing CD8+ T Cell Epitopes Conserved among Diverse Bovine Viral Diarrhea Virus Strains
BVDV-1– and -2–immunized cattle developed cross-reactive CD8+ T cells.
IFN-γ–inducing CD8+ T cell epitopes were identified from various BVDV Ags.
CD8+ T cell epitopes are highly conserved across >200 BVDV-1 and -2 strains.
The Regulatory Subunit PPP2R2A of PP2A Enhances Th1 and Th17 Differentiation through Activation of the GEF-H1/RhoA/ROCK Signaling Pathway
PPP2R2A promotes Th1 and Th17 but not Treg cell differentiation.
PPP2R2A deficiency impairs GEF-H1/RhoA/ROCK pathway in Th1 and Th17 cells.
PPP2R2A deficiency in T cells mitigates experimental autoimmune encephalomyelitis.
Mood Disorder in Systemic Lupus Erythematosus Induced by Antiribosomal P Protein Antibodies Associated with Decreased Serum and Brain Tryptophan
Antiribosomal P protein Abs induced depressive behavior and anxiety in mice.
Brain and serum tryptophan were decreased in mice with behavioral deficits.
Serum tryptophan was decreased in SLE patients with anti-P Abs or with NPSLE.
Characterization of a TNFR2-Selective Agonistic TNF-α Mutant and Its Derivatives as an Optimal Regulatory T Cell Expander
A TNFR2 agonist, R2agoTNF, selectively and preferentially expands Tregs in mice.
Structural optimization of R2agoTNF increased Tregs via enhanced TNFR2 signaling.
scR2agoTNF-Fc is a potential drug to suppress contact hypersensitivity.
Erythropoietin Protects against Diffuse Alveolar Hemorrhage in Mice by Regulating Macrophage Polarization through the EPOR/JAK2/STAT3 Axis
EPO exerts a significant therapeutic effect on the DAH murine model.
EPO protects against DAH by regulating macrophage polarization via the EPOR/JAK2/STAT3 axis.
The Ancient Cytokine BAFF- and APRIL-like Molecule Regulates the Functionality of Teleost IgM+ B Cells Similarly to BAFF and APRIL
BALM affects trout B cell functionality in a manner similar to BAFF and APRIL.
Evidence suggests that BALM signals through the same receptors as BAFF and APRIL.
PDK1 is required for Treg cell suppressive function.
PDK1-deficient Treg cells have impaired NF-κB signaling.
Forced activation of NF-κB rescues the phenotype of Foxp3YFP-cre Pdk1f/f mice.
Cross-Talk between the Complement Pathway and the Contact Activation System of Coagulation: Activated Factor XI Neutralizes Complement Factor H
FXIa cleaves CFH at the R341/R342 bonds at the end of the CCP 6 domain of CFH.
FXIa reduces CFH cofactor and decay‐accelerating activity and binding to ECs.
CFH binds FXI and inhibits FXI activation by either thrombin or FXIIa.
CD154 Resistant to Cleavage from Intracellular Milieu and Cell Surface Induces More Potent CD40-Mediated Responses
CD154-EM mutant is resistant to the spontaneous and induced cleavage from T cells.
Spontaneous and induced cleavage of CD154 from T cells is mediated by ADAM10/ADAM17.
The cleavage-resistant CD154 is a more prominent stimulant than cleavable CD154-WT.
IMMUNOTHERAPY AND VACCINES
Glycolipid-Containing Nanoparticle Vaccine Engages Invariant NKT Cells to Enhance Humoral Protection against Systemic Bacterial Infection but Abrogates T-Independent Vaccine Responses
Glycolipid-adjuvanted vaccine activates iNKT cells to support humoral immunity.
Nanoparticle delivery of glycolipids avoids iNKT anergy and allows adjuvant dose sparing.
iNKT cells can either support or suppress vaccine responses, depending on context.
Inclusion of an Optimized Plasmodium falciparum Merozoite Surface Protein 2–Based Antigen in a Trivalent, Multistage Malaria Vaccine
Construction of a PfMSP2/8 immunogen improved vaccine potential.
GLA-SE as adjuvant increased titer and functionality of vaccine-induced IgG.
Individual components of a trivalent malaria vaccine retained immunogenicity.
INFECTIOUS DISEASE AND HOST RESPONSE
OTUD1 deubiquitinates CARD9.
OTUD1 positively regulates CLR-induced signaling and cytokine production.
OTUD1 protects mice against C. albicans–induced fungal infection.
ASFV MGF-505-7R inhibits cGAS–STING signaling.
MGF-505-7R–deficient ASFV was fully attenuated in pigs at a dose of 10 HAD50.
Pinaverium Bromide Attenuates Lipopolysaccharide-Induced Excessive Systemic Inflammation via Inhibiting Neutrophil Priming
PVB inhibits GM-CSF–induced neutrophil priming.
PVB may be used “off-label” to improve the survival of patients with sepsis.
INNATE IMMUNITY AND INFLAMMATION
IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1–Induced Corneal Immunopathology
HSV-1 infection induces a strong IFN-λ response at the corneal epithelial surface.
IFN-λ differentially regulates antiviral and inflammatory responses in the cornea.
rIFN-λ treatment suppresses HSV-1–induced corneal immunopathology.
Heme induces oligomerization of caspase-1, caspase-4, and caspase-5.
Heme-induced IL-1β release requires both caspase-4 and caspase-5.
Caspase-4 is the primary effector of heme-induced cell death.
Loss of Mitochondrial Protease CLPP Activates Type I IFN Responses through the Mitochondrial DNA–cGAS–STING Signaling Axis
IFN-I signaling in CLPP-deficient cells and tissues depends on cGAS and STING.
CLPP-deficient cells are resistant to DNA and RNA viruses because of elevated ISGs.
CLPP-deficient cells exhibit mitochondrial DNA stress and release into the cytosol.
Mycobacterium smegmatis Resists the Bactericidal Activity of Hypochlorous Acid Produced in Neutrophil Phagosomes
M. smegmatis were killed by human neutrophils more slowly than other bacteria.
Phagosomal M. smegmatis kept their mycothiol reduced despite HOCl exposure.
Sensitizing mycobacteria to killing by HOCl would aid destruction by neutrophils.
Zebrafish caspy2–GSDMEb axis contributes to neutrophil pyroptosis in vivo.
Depletion of caspy2 or GSDMEb impairs the process of NETosis.
Pyroptosis-gated NETosis plays a critical role in teleost innate immunity.
Neutrophils actively internalize pulmonary surfactant during cigarette smoke exposure.
Absence of neutrophils alters surfactant homeostasis during smoking.
Absence of neutrophils exacerbates the proinflammatory response to smoking.
Cell stress induces the expression of EGOT via the PI3K/AKT, MAPK, and NF-κB pathways.
EGOT favors the expression of PI3K/AKT target genes required for cell proliferation.
EGOT supports TBLR1 expression, contributing to transcription of NF-κB target genes.
Human Inflammatory Neutrophils Express Genes Encoding Peptidase Inhibitors: Production of Elafin Mediated by NF-κB and CCAAT/Enhancer-Binding Protein β
LL neutrophils express genes of peptidase inhibitor families.
The PI3 gene encoding elafin is the most highly expressed gene by LL neutrophils.
Elafin is produced because of a synergism between GM-CSF and TNF via C/EBPβ and NF-κB.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Two Human Monoclonal HLA-Reactive Antibodies Cross-React with Mamu-B*008, a Rhesus Macaque MHC Allotype Associated with Control of Simian Immunodeficiency Virus Replication
Human HLA-reactive mAbs OK4F9 and OK4F10 cross-react to Mamu-B*008:01.
Human mAb MUS4H4 shows a more complex cross-reactivity in relation to Mamu allotypes.
Presence of IL-1α in melanoma makes the disease resistant to immunotherapy.
IL-1 pathway blockade enhances the efficacy of CD40 agonist therapy.
IL-1 pathway blockade improves response to therapy through elimination of PMN-MDSCs.
On the cover: CLPP-knockout (KO) cells are protected from vesicular stomatitis virus (VSV) due to elevated activation of the cGAS–STING signaling axis. Pictured are CLPP-KO/STING-KO mouse fibroblasts, which are highly susceptible to infection with VSV. VSV-G envelope glycoprotein appears in green, and cell nuclei appear in blue. Torres-Odio, S., Y. Lei, S. Gispert, A. Maletzko, J. Key, S. S. Menissy, I. Wittig, G. Auburger, and A. P.West. 2021. Loss of mitochondrial protease CLPP activates type I IFN responses through the mitochondrial DNA–cGAS–STING signaling axis. J. Immunol. 206: 1890–1900.
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