PILLARS OF IMMUNOLOGY
This Pillars of Immunology article is a commentary on “Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors,” a pivotal article written by E. A. Leadbetter, I. R. Rifkin, A. M. Hohlbaum, B. C. Beaudette, M. J. Shlomchik and A. Marshak-Rothstein, and published in Nature in 2002. https://www.nature.com/articles/416603a.
CLINICAL AND HUMAN IMMUNOLOGY
A functionally active SNP in the TOLLIP promoter is associated with decreased IL-12.
TOLLIP participates in DC maturation during M. tuberculosis infection.
Characterization of Mycobacterium tuberculosis–Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection
IL-22 is produced by conventional CD4+ T cells that require TCR engagement.
Th22 cells are markedly reduced during TB and HIV coinfection compared to Th1 cells.
Th22 cells exhibit shared and distinct features compared to Th1 and Th17 cells.
Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells
Carma3−/− mice show exacerbated liver injury in Con A–induced hepatitis model.
Carma3 deficiency causes increased mitochondria damage in LSEC upon Con A stimulation.
Heparin pretreatment can prevent Con A–induced liver injury.
Tolerogenic Immune-Modifying Nanoparticles Encapsulating Multiple Recombinant Pancreatic β Cell Proteins Prevent Onset and Progression of Type 1 Diabetes in Nonobese Diabetic Mice
T1D is initiated and driven by multiple diabetogenic CD4+ T cell epitopes.
Tolerance to individual epitopes/proteins fails to inhibit T1D development.
Tolerance to a cocktail of diabetogenic proteins inhibits T1D development.
Deacetylation of hemocyanin increases its LPS binding and antibacterial activity.
The K481/484 residues on hemocyanin are critical for binding with bacteria or LPS.
HDAC3 and TIP60 regulate the acetylation of hemocyanin on K481/484.
The Brucella Effector BspI Suppresses Inflammation via Inhibition of IRE1 Kinase Activity during Brucella Infection
BspI negatively regulates proinflammatory responses during Brucella infection.
BspI suppresses proinflammatory responses via the IRE1–TRAF2–NF-κB pathway.
BspI-inhibited NF-κB activation requires its GAP domain.
IMMUNE SYSTEM DEVELOPMENT
A Novel CD135+ Subset of Mouse Monocytes with a Distinct Differentiation Pathway and Antigen-Presenting Properties
A CD135+ subset was identified within mouse CD115+CD11b+ monocytes.
CD135+ monocytes exhibited Ag-presenting functions.
CD135+ monocytes were direct progeny of MDPs but not of cMoPs.
IMMUNOTHERAPY AND VACCINES
LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade
HVEM and LTβR are broadly expressed on tumor-infiltrating CD8+ T, NK, and myeloid cells.
LIGHT binding to HVEM/LTβR activates Fc-independent myeloid/T/NK cell activation.
TIGIT-Fc-LIGHT induces anti tumor responses in CPI primary/acquired resistant tumors.
Th2-Biased Transcriptional Profile Predicts HIV Envelope-Specific Polyfunctional CD4+ T Cells That Correlated with Reduced Risk of Infection in RV144 Trial
A novel multiplexed assay isolates polyfunctional T cells for downstream analyses.
We identified surface markers upregulated on vaccine-specific polyfunctional CD4 T cells.
A signature predicts a CD4 T cell profile correlated with reduced risk of HIV infection.
INFECTIOUS DISEASE AND HOST RESPONSE
A Baseline Cellular Antiviral State Is Maintained by cGAS and Its Most Frequent Naturally Occurring Variant rs610913
rs610913 is a frequent, nonsynonymous variant in the cGAS-encoding gene MB21D1.
cGAS(WT) and cGAS (P261H) maintain a baseline cellular antiviral state.
cGAS(WT) and cGAS (P261H) share similar DNA-sensing and antiviral capacities.
Neutrophils and monocytes produce IL-1α and IL-1β in P. aeruginosa–infected corneas.
P. aeruginosa is more rapidly killed in infected Il1a−/− compared with WT corneas.
Il1a−/− neutrophils have a more proinflammatory transcriptome with elevated C1q.
INNATE IMMUNITY AND INFLAMMATION
A Vitamin D–RelB/NF-κB Pathway Limits Chandipura Virus Multiplication by Rewiring the Homeostatic State of Autoregulatory Type 1 IFN–IRF7 Signaling
Vitamin D generates a cell state less permissive for Chandipura virus infections.
Vitamin D triggers autoregulatory T1-IFN–IRF7 signaling, basally.
Downmodulating RelB NF-κB, vitamin D provokes antiviral type 1 IFN signaling.
ICAM-1 Abundance Is Increased in Pancreatic Islets of Hyperglycemic Female NOD Mice and Is Rapidly Upregulated by NF-κB in Pancreatic β-Cells
Icam1 mRNA is elevated in islets from female versus male NOD mice.
ICAM-1 protein abundance is greater in hyperglycemic female NOD mice.
IL-1β rapidly upregulates expression of the Icam1 gene in β-cells.
Heat Shock Protein 70 Is a Damage-Associated Molecular Pattern That by Binding to Lipopolysaccharide and β-1,3-Glucan–Binding Protein Activates the Prophenoloxidase System in Shrimp
LvHSP70 promotes PRR expression of LvTRL2, LvTRL5, and LvLGBP.
LvHSP70 interacts with LvLGBP-driven innate immunity and activates the proPO system.
LvHSP70 acts as a DAMP and activates the proPO cascade by interacting with free LvLGBP.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Affinity-Driven Site-Specific High Mannose Modification Determines the Structural Polymerization and Function of Tetrameric IgM in a Primitive Vertebrate
Ag immunization significantly upregulates the tilapia IgM Ab affinity.
Affinity influences the isomeric structure and high mannose modification of IgM.
High-affinity IgM plays an important role in regulating phagocytosis.
Human macrophages infiltrate human melanoma in mice, which is associated with metastasis.
Tumor-infiltrating macrophages have a unique transcriptional signature.
Similar macrophages are found in melanoma patient samples.
PPP2R2D Suppresses Effector T Cell Exhaustion and Regulatory T Cell Expansion and Inhibits Tumor Growth in Melanoma
PPP2R2D limits T cell exhaustion by controlling chromatin accessibility.
PPP2R2D deficiency in T cells promotes tumor growth of melanoma.
PPP2R2D deficiency in T cells expands the Treg population in tumor-infiltrating T cells.
The NKG2A/Qa-1b axis inhibits RT-induced T cell responses.
Combined RT plus NKG2A/PD-1 blockade improved survival in B16F10 tumors.
On the cover: Intravital imaging of the liver vascular structure via i.v. injection of anti-CD31 fluorescence Ab (red) and FITC-labeled Con A (green). Cheng, L., Z. Wei, Z. Yang, R. Lu, M. Yang, M. Yu, N. Yang, S. Li, M. Gao, X. Zhao, and X. Lin. 2022. Carma3 protects from liver injury by preserving mitochondrial integrity in liver sinusoidal endothelial cells. J. Immunol. 209: 456–464.
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