IN THIS ISSUE
Tracing Antiviral CD8+ T Cell Responses Using In Vivo Imaging
Cutting Edge: TAK1 Safeguards Macrophages against Proinflammatory Cell Death
TAK1 protects macrophages from proinflammatory cell death in TLR and TNFRI signaling.
The cell death machinery is dependent on active caspases and GSDMD processing.
TAK1 in macrophages both positively and negatively controls host inflammatory responses.
Cutting Edge: CXCR3 Escapes X Chromosome Inactivation in T Cells during Infection: Potential Implications for Sex Differences in Immune Responses
A bicistronic dual-reporter mouse enables visualization of allelic CXCR3 expression.
CXCR3 escapes X chromosome inactivation (XCI) in T cells in vivo during infection.
XCI escape by CXCR3 potentially contributes to enhanced Th1 responses in females.
Cutting Edge: Protein Arginine Deiminase 2 and 4 Regulate NLRP3 Inflammasome–Dependent IL-1β Maturation and ASC Speck Formation in Macrophages
Citrullination in macrophages is induced during pyroptosis.
The NLRP3 inflammasome is regulated by Ca2+-dependent PAD enzymes.
Cutting Edge: Tcf1 Instructs T Follicular Helper Cell Differentiation by Repressing Blimp1 in Response to Acute Viral Infection
Tcf1-mediated repression of Blimp1 is functionally critical for TFH differentiation.
An intron-3 regulatory region in the Blimp1 gene is necessary for optimal TFH response.
Cutting Edge: Bacillus Calmette–Guérin–Induced T Cells Shape Mycobacterium tuberculosis Infection before Reducing the Bacterial Burden
BCG immunization alters the cell types targeted for early M. tuberculosis infection.
Vaccine-induced CD4 T cells are required for this transfer of infection.
T cell activation within the lung first occurs distal to sites of infection.
ALLERGY AND OTHER HYPERSENSITIVITIES
Cutaneous Exposure to Clinically Relevant Lone Star Ticks Promotes IgE Production and Hypersensitivity through CD4+ T Cell– and MyD88-Dependent Pathways in Mice
Lone star tick proteins induce IgE production and hypersensitivity reactions in mice.
CD4+ T cell help is required for both sensitization and recall IgE production.
MyD88 deficiency in B cells disrupts IgE production.
ANTIGEN RECOGNITION AND RESPONSES
Allogenicity Boosts Extracellular Vesicle–Induced Antigen-Specific Immunity and Mediates Tumor Protection and Long-Term Memory In Vivo
Injection of allogeneic Ag-loaded EVs significantly increases IgG in mice.
Two injections of syngeneic or allogeneic EVs result in long-term immunity.
Syngeneic and allogeneic EVs are equally potent in inhibiting tumor growth.
Conditional Upregulation of IFN-α Alone Is Sufficient to Induce Systemic Lupus Erythematosus
We studied whether and to what extent IFN-α causes SLE.
We found that increase of IFN-α alone was sufficient to cause SLE.
The DNT cells as expanded by IFN-α directly caused organ manifestation of SLE.
Programmed Death-1 Restrains the Germinal Center in Type 1 Diabetes
PD-1 blockade or deficiency unleashes follicular insulin-specific CD4+ T and B cells.
PD-1 limits T follicular helper cell survival in the germinal center.
PD-1 blockade increases insulin autoantibody production in diabetes-prone mice.
CLINICAL AND HUMAN IMMUNOLOGY
Cholesterol Crystals Induce Coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor
Cholesterol crystals induce coagulation through monocyte TF.
Monocyte TF induction is blocked by complement inhibitors to C3, C5, or C5aR1.
Monocyte TF induction is dependent on complement C5aR1.
Cyclooxygenase-1 Regulates the Development of Follicular Th Cells via Prostaglandin E2
COX-1 deficiency impaired TFH cell development during influenza infection and KLH immunization.
COX-1–derived metabolite PGE2 and its receptors EP2/EP4 mediate the effect of COX-1 on TFH cells.
Identification of the E3 Ligase TRIM29 as a Critical Checkpoint Regulator of NK Cell Functions
TRIM29 is induced in NK cells and inhibits NK functions.
TRIM29 deletion in NK cells enhances IFN-γ production.
TRIM29 ubiquitinates and degrades TAB2 in activated NK cells.
IMMUNE SYSTEM DEVELOPMENT
TCR Affinity for In Vivo Peptide-Induced Thymic Positive Selection Fine-Tunes TCR Responsiveness of Peripheral CD8+ T Cells
In vivo administration of a peptide can promote T cell selection in the thymus.
Affinity for TCR/pMHC during positive selection fine-tunes peripheral T cells.
IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis
MS-associated SNP rs17066096 influences IL-22BP levels.
IL-22BP promotes neuroinflammation by blocking IL-22 signaling.
IL-22 reduces T cell IFN-γ production.
IMMUNOTHERAPY AND VACCINES
Kynurenine 3-Monooxygenase Inhibition during Acute Simian Immunodeficiency Virus Infection Lowers PD-1 Expression and Improves Post–Combination Antiretroviral Therapy CD4+ T Cell Counts and Body Weight
KMO inhibition improved clinical outcomes of CD4+ T cell counts and body weight.
KMO inhibition increased naive T cell frequency and lowered PD-1 expression.
INFECTIOUS DISEASE AND HOST RESPONSE
IL-1β Induces the Rapid Secretion of the Antimicrobial Protein IL-26 from Th17 Cells
TLR ligands induce IL-26 secretion from PBMCs in an IL-1β–dependent manner.
IL-1β induces rapid IL-26 release by IL-1RI+ Th17 cells without TCR activation.
IL-1β–stimulated T cells mediate an antimicrobial activity via IL-26.
IL-36γ Promotes Killing of Mycobacterium tuberculosis by Macrophages via WNT5A-Induced Noncanonical WNT Signaling
IL-36γ conferred MDMs M. tuberculosis resistance through activation of autophagy.
IL-36γ induced autophagy relying on WNT5A/COX-2/AKT/mTOR axis.
IL-36γ may be a potential candidate for immune therapy of tuberculosis.
The Impact of TCR Signal Strength on Resident Memory T Cell Formation during Influenza Virus Infection
Low affinity–stimulated CD8+ T cells have an advantage in forming TRM.
High and low affinity–stimulated TRM have distinct transcriptomes.
TRM longevity is not impacted by strength of TCR stimulation.
The Functional Requirement for CD69 in Establishment of Resident Memory CD8+ T Cells Varies with Tissue Location
CD69 is not required for the establishment of CD8+ TRM in every nonlymphoid tissue.
In the kidney, CD69 is required for CD8+ TRM regardless of immunization approach.
CD69 deficiency prevents generation of KLF2low TRM in the kidney.
The Metabolic Cytokine Adiponectin Inhibits Inflammatory Lung Pathology in Invasive Aspergillosis
Adiponectin KO mice show increased pathology in a mouse model of IA.
KO mice show increased inflammatory and decreased anti-inflammatory phenotypes.
Increased lung inflammation in KO mice is independent of invasive fungal growth.
NK Cells Are Critical for Optimal Immunity to Experimental Trypanosoma congolense Infection
Deficiency of NK cells leads to enhanced susceptibility to T. congolense infection.
NK cells mediate protection during T. congolense infection via perforin.
A Subset of Mycobacteria-Specific CD4+ IFN-γ+ T Cell Expressing Naive Phenotype Confers Protection against Tuberculosis Infection in the Lung
We describe a naive-like M. tuberculosis–specific CD4+ IFN-γ+ memory T cell (TNLM).
TNLM provide protection equal to known memory subsets against M. tuberculosis lung infection.
INNATE IMMUNITY AND INFLAMMATION
KLF12 Regulates Mouse NK Cell Proliferation
KLF12 deficiency does not affect NK cell development and effector functions.
KLF12-deficient NK cells have increased expression of Btg3 and the IL-21 receptor.
IL-21 induced Btg3 and inhibited KLF12-deficient NK cell proliferation.
Tim-4 Inhibits NLRP3 Inflammasome via the LKB1/AMPKα Pathway in Macrophages
NAFLD microenvironments increase Tim-4 expression in macrophages.
Tim-4 in macrophages suppresses NLRP3 inflammasome depending on PS binding motif.
Tim-4 promotes phosphorylation of AMPKα by interacting with LKB1.
NAC1 Potentiates Cellular Antiviral Signaling by Bridging MAVS and TBK1
NAC1 enhances the virus-induced IFN signaling and activation of TBK1 and IRF3.
NAC1 inhibits the replication of RNA viruses.
NAC1 promotes the recruitment of TBK1 to MAVS upon viral infection.
Noncanonical Role of FBXO6 in Regulating Antiviral Immunity
FBXO6 can negatively regulate the activation of IFN-I signaling.
FBXO6 interacts with and mediates IRF3 degradation independent of SCF complex.
Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-κB Signaling Pathways
AZM’s immunomodulatory mechanism involves both NF-κB and STAT1 pathways.
AZM’s impact on STAT1 phosphorylation works in part through IKKβ.
Vacuolar (H+)-ATPase Critically Regulates Specialized Proresolving Mediator Pathways in Human M2-like Monocyte-Derived Macrophages and Has a Crucial Role in Resolution of Inflammation
V-ATPase is required for ERK-mediated 15-LOX-1 expression during M2 polarization.
Inhibition of V-ATPase prevents 15-LOX-1–mediated SPM biosynthesis in M2 macrophages.
Targeting V-ATPase delays resolution in murine peritonitis with decreased SPM levels.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Early T-BET Expression Ensures an Appropriate CD8+ Lineage–Specific Transcriptional Landscape after Influenza A Virus Infection
Early T-BET expression is important for early acquisition of CD8+ T cell lineage–specific function.
T-BET expression shuts down inappropriate T cell lineage functions in activated CD8+ T cells.
Early T-BET expression is required for activation of specific IFN-γ transcriptional enhancers.
Carboxyl-Terminal Src Kinase Binds CD28 upon Activation and Mutes Downstream Signaling
The interactomes of CD2 and CD28 were identified.
CSK is a specific and direct interactor of activated CD28.
CSK regulates signaling downstream of CD28.
Semiquantitative Proteomics Enables Mapping of Murine Neutrophil Dynamics following Lethal Influenza Virus Infection
Neutrophil proteomes are mapped during homeostasis or following lethal PR8 infection.
ISGs are first elevated in BM and then BAL neutrophils following lethal PR8 infection.
BAL neutrophil proteomes exhibit a modest capacity for pathogen tuning.
LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells
LILRB1 inhibits BiTE molecule–induced cytolytic activity of human CD8+ T cells.
LILRB1 and PD1 express on distinct human CD8+ T cell subsets in tumors.
LILRB1 and PD1 blockades have synergistic effects to enhance CD8+ T cell activity.
On the cover: Monocytes and cholesterol crystals (CC) are found in an intracranial thrombus retracted from a patient with advanced carotid atherosclerosis. Frozen section stained with anti-CD14/DAB and explored with polarization filter reflected light microscopy revealing birefringent CC structures using an Olympus XC30 CCD color camera, 40× objective. Gravastrand, C. S., B. Steinkjer, B. Halvorsen, A. Landsem, M. Skjelland, E. A. Jacobsen, T. M. Woodruff, J. D. Lambris, T. E. Mollnes, O.-L. Brekke, T. Espevik, and A. M. A. Rokstad. 2019. Cholesterol crystals induce coagulation activation through complement-dependent expression of monocytic tissue factor. J. Immunol. 203: 853–863.
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