PILLARS OF IMMUNOLOGY
This Pillars of Immunology article is a commentary on “A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation,” a pivotal article written by Y.-H. Chien, M. Iwashima, K. B. Kaplan, J. F. Elliott, and M. M. Davis, and published in Nature, in 1987. https://www.nature.com/articles/327677a0.
ALLERGY AND OTHER HYPERSENSITIVITIES
Mice Expressing Cosegregating Single Nucleotide Polymorphisms (D298G and N397I) in TLR4 Have Enhanced Responses to House Dust Mite Allergen
Severity of asthma in TLR4-SNP mice is dependent on the allergen system.
TLR4-SNP mice have reduced allergic inflammation when using the OVA-LPS model.
TLR4-SNP mice have enhanced allergic responses when using the HDM model.
Lupus B cells present an elevated metabolism preceding the onset of autoimmunity.
Except for GC B cells, glucose largely drives the metabolism of lupus B cells.
Lupus and control B cells require glycolysis and glutaminolysis in TI responses.
Adipocyte CD1d Gene Transfer Induces T Cell Expansion and Adipocyte Inflammation in CD1d Knockout Mice
AAV-mediated CD1d gene delivery to CD1d knockout mouse fails to rescue iNKT cells.
Reintroducing adipocyte CD1d induces massive expansion of adipose T cells.
CD8+ T cells induced by adipocyte CD1d cause adipocyte NLRP3 inflammasome activation.
Essential Roles of the Transcription Factor NR4A1 in Regulatory T Cell Differentiation under the Influence of Immunosuppressants
Nr4a1 plays crucial roles in Treg cell differentiation in the presence of CNIs.
Nr4a1 deficiency impairs the induction of T cell tolerance in the presence of CNIs.
IMMUNE SYSTEM DEVELOPMENT
Most γδ recent thymic emigrants are immature.
Some γδ T cells complete maturation in the thymus, and others complete maturation in the periphery.
A population of γδ thymocytes is thymic resident.
Somatic Diversification of Rearranged Antibody Gene Segments by Intra- and Interchromosomal Templated Mutagenesis
Novel computational script TRACE can detect gene conversion from across the genome.
TRACE detects gene conversion donors from both intra- and interchromosomal sources.
TRACE outputs correlate with germinal center B cell physiology.
INFECTIOUS DISEASE AND HOST RESPONSE
Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection
CD4+ and CD8+ T cells show high but distinct longitudinal responses in pH1N1 patients.
Expression of immune checkpoints on CD4+ and CD8+ T cells changed after pH1N1 infection.
INNATE IMMUNITY AND INFLAMMATION
LL-37 induces cell death in autophagy-dysfunctional endothelial cells.
Under this condition, the intracellular degradation of LL-37 is disturbed.
Neutrophil Protein Kinase R Mediates Endothelial Adhesion and Migration by the Promotion of Neutrophil Actin Polymerization
Inhibition of neutrophil PKR suppresses neutrophil adhesion and migration.
Genetic silencing of PKR diminishes CaMKII activation and actin polymerization.
PKR inhibition suppresses neutrophil recruitment in mouse inflammatory diseases.
eCIRP is released through GSDMD pores independent of pyroptotic cell death.
GSDMD and eCIRP interact with each other and colocalize at the cell membrane.
Targeting GSDMD by a pharmacological approach inhibits eCIRP release in sepsis.
Zebrafish CERKL Enhances Host TBK1 Stability and Simultaneously Degrades Viral Protein via Ubiquitination Modulation
CERKL mediates protection against viral infection via two distinct mechanisms.
CERKL specifically stabilizes TBK1 by impeding the K48-linked polyubiquitination.
CERKL decreases SVCV P protein though preventing K63-linked polyubiquitination.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Diverse binding properties are revealed for seven nanobodies against C4b.
Cryo-electron microscopy structures of C4b–nanobody complexes indicate nanobodies’ modes of action.
Nanobodies have therapeutic potential and are useful for labeling studies.
Somatic hypermutation in four JH and four Jκ introns extends for approximately 1 kb.
Intron DNA sequences and enhancers do not delimit the 3′ boundary of SHM.
V regions are likely targeted for mutation by proximity to the promoter.
NK cellular response is inhibited by ovarian cancer patient ascites.
Ascites alters NK cell gene expression involved in activation and cytotoxicity.
CA125, found in high concentrations in ascites, inhibits NK cell function.
IL-27 signaling directly induces CCL5 production by mouse and human T cells.
Stat3 and Stat1 bind to the CCL5 promoter in IL-27–stimulated CD8+ T cells.
IL-27–induced CCL5 production enhances antitumor activity.
NOVEL IMMUNOLOGICAL METHODS
A Single-Domain TCR-like Antibody Selective for the Qa-1b/Qdm Peptide Complex Enhances Tumoricidal Activity of NK Cells via Blocking the NKG2A Immune Checkpoint
A llama was immunized with Qa-1b/Qdm, ligand for NKG2A, to construct a VHH library.
A single-domain TCR-like Ab, EXX-1, specific for Qa-1b/Qdm, was identified.
EXX-1 selectively blocks the NKG2A/Qa-1b axis to promote NK lysis of target cells.
On the cover: Lung sections from C57BL/6 mice expressing single nucleotide polymorphisms (SNPs) in TLR4 (TLR4-SNP) treated with house dust mite (HDM) extract were immunostained with an anti-YM1 Ab and visualized under oil using a × 100 objective. YM1 staining revealed that TLR4-SNP mice had dramatically increased YM1 positivity after HDM treatment. Fink, M. Y., X.Qi, K. A. Shirey, R. Fanaroff, S. Chapoval, R.M. Viscardi, S. N. Vogel, and A.D. Keegan. 2022.Mice expressing cosegregating single nucleotide polymorphisms (D298G and N397I) in TLR4 have enhanced responses to house dust mite allergen. J. Immunol. 208: 2085–2097.
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