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PILLARS OF IMMUNOLOGY
CUTTING EDGE
Cutting Edge: Low-dose Recombinant IL-2 Treatment Prevents Autoantibody Responses in Systemic Lupus Erythematosus via Regulatory T Cell–independent Depletion of T Follicular Helper Cells
IL-2 treatment depletes autoreactive Tfh cells in SLE.
IL-2 depletion of Tfh cells does not require Tregs.
ANTIGEN RECOGNITION AND RESPONSES
An Integrated Signaling Threshold Initiates IgG Response toward Virus-like Immunogens
High ED on virus-like immunogens induces IgG independent of T cells or TLR activation.
CD19 is required for Ab responses toward virus-like immunogens without iNAs.
iNAs reduce the threshold of ED required for individual B cells to initiate IgG.
CLINICAL AND HUMAN IMMUNOLOGY
CD9 and Aryl Hydrocarbon Receptor Are Markers of Human CD19+CD14+ Atypical B Cells and Are Dysregulated in Systemic Lupus Erythematous Disease
CD14+ atypical B cells are consistently detected in healthy human PBMCs.
atB cells express AHR and upregulate CD14 and CD9 in response to CpG-ODN.
CD9+CD14+ B cells are phagocytic, and loss of CD9 is negatively associated with SLEDAI.
Orientation Regulation of Class-switch Recombination in Human B Cells
CSR is programmed for deletional recombination in human B cells.
The efficiency of c-NHEJ and S region features affects the orientation of CSR in humans.
Sequence Matters: Primary COVID-19 Vaccination after Infection Elicits Similar Anti-spike Antibody Levels, but Stronger Antibody Dependent Cell-mediated Cytotoxicity than Breakthrough Infection
Omicron breakthrough infection induces IgA and IgG anti-S levels similar to hybrid immunity.
Hybrid immunity elicits higher levels of ADCC than breakthrough infection.
Robust ADCC is associated with a differential IgG reactivity pattern across Spike.
IMMUNE REGULATION
Ebi3 Binding to IFN-γ and IL-10 Limits Their Function
Treg-restricted deletion of Ebi3 or p35 has a differential effect on the tumor microenvironment.
Ebi3 can bind to cytokines outside of the IL-12 cytokine family.
Ebi3 exhibits binding to IL-10 and IFN-γ and blocks their signaling and function.
Understanding the Role of miR-29a in the Regulation of RAG1, a Gene Associated with the Development of the Immune System
miR-29a, along with miR-29c, regulates RAG1 expression in B cells of mice and humans.
Overexpression of miR-29a decreases V(D)J recombination in pro-B cells of mice.
miR-29a exerts a substantial impact on mice immunity and survival.
CPT2-mediated Fatty Acid Oxidation Is Dispensable for Humoral Immunity
CPT2 is required for LCFA oxidation and mitochondrial metabolism in B cells.
Chronic or acute deletion of CTP2 does not affect B cell activation in vitro.
CPT2 deficiency does not affect humoral immunity in vivo.
IMMUNOGENETICS
Anti–Heat Shock Protein 70 Autoantibodies from Patients with Idiopathic Pulmonary Fibrosis Epigenetically Enhance Lung Fibroblast Apoptosis Resistance and Bcl-2 Expression
HSP70 autoantibodies from patients with IPF increase lung fibroblast apoptosis resistance.
Bcl-2 is upregulated in HSP70 autoantibody-treated fibroblasts.
The increased Bcl-2 expression is through enriched binding with H4K16Ac.
INFECTIOUS DISEASE AND HOST RESPONSE
Maternal Helminth Infection Causes Dysfunctional B Cell Development in Male Offspring
Pups from infected mothers have decreased IL-7 secretion in the bone marrow.
Males from infected mothers have a sex-specific defect in the B cell development.
Defects in male B cell development during maternal infection alter vaccine responses.
Glucocorticoid-mediated Suppression of Effector Programming Assists the Memory Transition of Virus-specific CD8+ T Cells
Basal GR signaling is crucial for optimal memory differentiation.
GR blockade and genetic depletion perturbed memory transition and homeostatic turnover of CD8+ T cells.
A low dose of GCs reduced cellular ROS levels and enhanced Bcl2 expression in effector cells.
Febrile Temperature Acts through HSP70–Toll4 Signaling to Improve Shrimp Resistance to White Spot Syndrome Virus
High temperatures (32°C water) significantly inhibit WSSV replication and pathogenicity.
HSP70 plays a crucial protective role against WSSV at elevated temperatures (32°C).
The HSP70–Toll4–Dorsal–AMP signaling axis confers protection against WSSV infection at 32°C.
IFN Receptor 2 Regulates TNF-α–Mediated Damaging Inflammation during Aspergillus Pulmonary Infection
Absence of IFNAR2 contributes to an Aspergillus-permissive lung environment.
IFNAR2 is required to prevent TNF-α–mediated damage during Aspergillus infection.
INNATE IMMUNITY AND INFLAMMATION
MAFB in Macrophages Regulates Prostaglandin E2–Mediated Lipid Mediator Class Switch through ALOX15 in Ischemic Acute Kidney Injury
Macrophage-specific Mafb-deficient mice showed poor prognosis of AKI.
AKI-driven ALOX15 induction was impaired in macrophage-specific Mafb-deficient mice.
MAFB in macrophages regulates ALOX15 expression under the COX-2/PGE2/EP4 pathway.
Potential Contributions of Human Endogenous Retroviruses in Innate Immune Memory
Macrophages under different states display specific HERV expression patterns.
HERVs provide potential transcriptional regulatory elements in trained macrophages.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Structure of a Human Monoclonal Antibody in Complex with Outer Surface Protein C of the Lyme Disease Spirochete, Borreliella burgdorferi
OspC is a virulence factor of the Lyme disease spirochete, Borreliella burgdorferi.
We report the first structure of OspC in complex with a human mAb.
Molecular insights into Ab responses associated with Lyme disease are revealed.
TUMOR IMMUNOLOGY
ITPK1 Sensitizes Tumor Cells to IgA-dependent Neutrophil Killing In Vivo
A novel approach reveals tumor intrinsic factors regulating neutrophil killing.
ITPK1 sensitizes IgA-opsonized tumor cells to killing by neutrophils in vivo.
The effect of ITPK1 depends on its kinase domain.
TLR7-Induced Mitochondrial Reactive Oxygen Species Production in Monocyte-derived Dendritic Cells Drives IL-12–Dependent NK Cell Activation and Enhances Antitumor Immunity
TLR7 activation in monocyte-derived DCs triggers mROS, boosting IL-12 secretion.
TLR7/mROS/IL-12 axis drives potent NK cell responses via imiquimod-activated DCs.
TLR7-activated DCs utilize MyD88-independent NF-κB signaling pathway to secrete IL-12.
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Cover Image
Cover Image
On the cover: GMS–stained lung sections of type I interferon receptor 1 deficient mice (Ifnar1–/–) showing increased hyphal growth following TNF-a treatment during infection with Aspergillus fumigatus, phenocopying what occurs in Ifnar2–/– mice (Aspergillus=black; tissue=green). These results support that absence of IFN receptor 2 subunit (IFNAR2) contributes to an Aspergillus permissive environment through dysregulation of inflammation. Rynda-Apple, A., J. Reyes Servin, J. Lenz, J. Roemer, E. E. Benson, M. N. Hall, and K. M. Shepardson. 2024. IFN receptor 2 regulates TNF-⍺–mediated damaging inflammation during Aspergillus pulmonary infection. J. Immunol. 213: 1202–1211.
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