PILLARS OF IMMUNOLOGY
This Pillars of Immunology article is a commentary on “Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade,” a pivotal article written by D. L. Sylvestre and J. V. Ravetch, and published in Science, in 1994. https://www.science.org/doi/10.1126/science.8066448.
Cutting Edge: Effect of Disease-Modifying Therapies on SARS-CoV-2 Vaccine–Induced Immune Responses in Multiple Sclerosis Patients
Anti-CD20 DMTs cause an absence of Spike-specific Abs and limit TFH frequency in MS patients.
Dimethyl fumarate causes a reduction in anti-Spike–specific CD8 T cells in MS patients.
Fingolimod compromises Spike-specific Ab and T cell responses in MS patients.
ALLERGY AND OTHER HYPERSENSITIVITIES
PRMT5 in T Cells Drives Th17 Responses, Mixed Granulocytic Inflammation, and Severe Allergic Airway Inflammation
Arginine methylation catalyzed by PRMT5 is increased during lung inflammation.
PRMT5 in T cells is required for severe eosinophilic/neutrophilic lung inflammation.
PRMT5 promotes high pulmonary sterol metabolic activity, RORγt, and Th17 responses.
T Cell–Specific Deletion of TRAIL Receptor Reveals Its Critical Role for Regulating Pathologic T Cell Activation and Disease Induction in Experimental Autoimmune Encephalomyelitis
T cell–specific TRAIL-R KO mice resist TRAIL-mediated anti-inflammation in EAE.
TRAIL directly inhibits T cell activation without inducing cell apoptosis in EAE.
TRAIL-R signaling significantly downregulates the genes of TCR signaling pathways.
Chlorzoxazone Alleviates Experimental Autoimmune Encephalomyelitis via Inhibiting IL-6 Secretion of Dendritic Cells
Chlorzoxazone reduced Th17 differentiation in the spleen and CNS in EAE mice.
Chlorzoxazone inhibited IL-6 production by DCs in a dose-dependent manner.
Chlorzoxazone affected the function of DCs through the AMPK pathway.
Pharmacologically Enhanced Regulatory Hematopoietic Stem Cells Revert Experimental Autoimmune Diabetes and Mitigate Other Autoimmune Disorders
Pharmacological modulation of HSC generated HSC.Regs.
HSC.Regs trafficked to the sites of inflammation.
HSC.Regs mitigated autoimmune responses (diseases).
Preclinical Analysis of Candidate Anti-Human CD79 Therapeutic Antibodies Using a Humanized CD79 Mouse Model
Anti-human CD79A prevents autoimmunity in mice without significant B cell depletion.
Anti-human CD79A induces a transient form of B cell anergy.
Anti-human CD79A may silence Ab production by plasmablasts and plasma cells.
Conventional NK Cells and Type 1 Innate Lymphoid Cells Do Not Influence Pathogenesis of Experimental Glomerulonephritis
The murine kidney harbors two distinct populations of NCR+T-bet+ ILCs.
Transcriptomic profiling identifies these two populations as cNK cells and ILC1s.
Depletion of NCR+T-bet+ ILCs does not influence pathogenesis of experimental cGN.
CLINICAL AND HUMAN IMMUNOLOGY
IL-22 Plays a Dual Role in the Amniotic Cavity: Tissue Injury and Host Defense against Microbes in Preterm Labor
IL-22 plays a dual role in the amniotic cavity.
IL-22 causes fetal tissue injury leading to neonatal death.
IL-22 participates in host defense against infection leading to preterm birth.
IL-2 Signaling Couples the MAPK and mTORC1 Axes to Promote T Cell Proliferation and Differentiation in Teleosts
Fish IL-2 participates in the clearance of bacteria by regulating the T cell response.
Fish IL-2 possesses an uncanonical receptor complex (IL-15Rα/IL-2Rβ/γc).
Fish IL-2 signaling couples MAPK and mTORC1 axes to regulate T cell immunity.
Structural Determinants in the Staphylococcus aureus–Derived Phenol-Soluble Modulin α2 Peptide Required for Neutrophil Formyl Peptide Receptor Activation
Neutrophils and FPR knock-in/knockout cells provide insights into receptor recognition.
The S. aureus peptide PSMα2 is an FPR2 agonist that triggers biased signaling.
Peptide parts that confer FPR1/FPR2 selectivity and alter signaling are identified.
TLT-1 Promotes Platelet–Monocyte Aggregate Formation to Induce IL-10–Producing B Cells in Tuberculosis
PMAs were increased in blood of patients with active TB.
TLT-1 was required for generation of PMAs.
PMAs were involved in B10 polarization.
IMMUNE SYSTEM DEVELOPMENT
Defects in Long-Term APC Repopulation Ability of Adult Human Bone Marrow Hematopoietic Stem Cells (HSCs) Compared with Fetal Liver HSCs
aBM HSCs expand in aBM-transplanted mice.
aBM CD34+ cells show less durable APC reconstitution than FL CD34+ cells.
Cytokine/niche support and intrabone injection improve APC reconstitution from aBM.
INFECTIOUS DISEASE AND HOST RESPONSE
Syk is critical for neutrophil response to Candida albicans.
LPS is capable of rescuing fungicidal activity in Syk-deficient neutrophils.
Restoration of fungicidal activity is in part due to activation of c-Fos.
Cytosolic Sensing of Intracellular Staphylococcus aureus by Mast Cells Elicits a Type I IFN Response That Enhances Cell-Autonomous Immunity
Staphylococcus aureus can internalize and survive within the human mast cells.
Mast cells produce type I IFN in response to intracellular S. aureus.
Type I IFN enhances cell-autonomous immunity in human mast cells.
The Extracellular ATP Receptor P2RX7 Imprints a Promemory Transcriptional Signature in Effector CD8+ T Cells
Effector CD8+ T cells with increased memory potential express higher P2RX7 levels.
P2RX7hi early effectors form memory CD8+ T cells with increased longevity.
P2RX7 favors the memory CD8+ T cell fate via TGF-β–mediated Zeb2 downregulation.
CRISPR/Cas9-Mediated Insertion of HIV Long Terminal Repeat within BACH2 Promotes Expansion of T Regulatory–like Cells
HIV integration frequently targets the intron preceding the first exon of BACH2.
Gene editing was used to model the impact of integration in primary CD4+ T cells.
BACH2 IS targeting led to selective expansion of a Treg–like population.
Participant age was positively associated with SARS-CoV-2 Ab levels in outpatients.
Participant BMI was positively correlated with SARS-CoV-2 Ab levels in outpatients.
Ab levels were associated with microneutralization activity against SARS-CoV-2.
An Epidemic Zika Virus Isolate Drives Enhanced T Follicular Helper Cell and B Cell–Mediated Immunity
Infection with ZIKVBR induces a dampened Th1 response.
Infection with ZIKVBR drives an enhanced Tfh/GC B cell response.
Abs induced by ZIKVBR are of higher avidity and neutralize infection better
INNATE IMMUNITY AND INFLAMMATION
Activated Platelets Upregulate β2 Integrin Mac-1 (CD11b/CD18) on Dendritic Cells, Which Mediates Heterotypic Cell–Cell Interaction
Platelet GPIbα interacts with Mac-1 on DCs.
For binding, P-selectin–PSGL1 interaction induces Mac-1 upregulation on DCs.
Influence of Self–MHC Class I Recognition on the Dynamics of NK Cell Responses to Cytomegalovirus Infection
Naive C57BL/6 mice have a pre-existing memory-like NK cell population.
The pre-existing memory-like population comprises predominantly licensed NK cells.
Ly49I has limited direct effect on NK cell responses to MCMV beyond proliferation.
Aged female, not male, mice maintain protective antipneumococcal natural Abs.
CD5+ B-1 cells from aged female and male mice differ in repertoire.
Sex influences the number, phenotype, and gene expression of CD5+ B-1 cells.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
GalNAc-conjugated C3 siRNA inhibits C3 gene expression in the liver of Cfh+/− mice.
C3 siRNA reduces plasma C3 fragmentation and factor B activation in Cfh+/− mice.
C3 siRNA limits glomerular C3 deposits in Cfh+/− mice.
NLRP1B and NLRP3 Control the Host Response following Colonization with the Commensal Protist Tritrichomonas musculis
The gut commensal Tritrichomonas musculis elevates luminal extracellular ATP levels.
NLRP1B and NLRP3 direct the Tritrichomonas musculis–driven Th cell response.
Common and Divergent Features of T Cells from Blood, Gut, and Genital Tract of Antiretroviral Therapy–Treated HIV+ Women
CyTOF was performed on matched blood, gut, and genital T cells from ART-suppressed HIV+ women.
Shared and distinct phenotypic features of T cells are observed from gut and genital tracts.
Gut has more Trm, but genital Trm cells preferentially express PD1.
Combinatorial Expression of NK Cell Receptors Governs Cell Subset Reactivity and Effector Functions but Not Tumor Specificity
Combinatorial expression of receptors dictates NK cell reactivity against tumors.
Hierarchy of response against different tumors is conserved among NK cell subsets.
NK cell subsets with relative effector specialization are defined.
NeoScore Integrates Characteristics of the Neoantigen:MHC Class I Interaction and Expression to Accurately Prioritize Immunogenic Neoantigens
MHC class I binding, stability, and expression predict neoantigen immunogenicity.
These characteristics were integrated into the NeoScore to rank immunogenicity.
A high NeoScore is associated with improved response to melanoma immunotherapy.
On the cover: Colorized field emission scanning electron microscopy photograph showing Staphylococcus aureus bacteria (red) in the process of internalizing within a human mast cell (blue). Goldmann, O., T. Sauerwein, G. Molinari, M. Rohde, K. U. Förstner, and E. Medina. 2022. Cytosolic sensing of intracellular Staphylococcus aureus by mast cells elicits a type I IFN response that enhances cell-autonomous immunity. J. Immunol. 208: 1675–1685.
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