Cutting Edge: EPHB2 Is a Coreceptor for Fungal Recognition and Phosphorylation of Syk in the Dectin-1 Signaling Pathway
EPHB2 is a coreceptor for the recognition of β-glucan in macrophages.
EPHB2 is a kinase for Syk and is required for Syk phosphorylation and activation.
ANTIGEN RECOGNITION AND RESPONSES
Mucosal-Associated Invariant T Cell Effector Function Is an Intrinsic Cell Property That Can Be Augmented by the Metabolic Cofactor α-Ketoglutarate
MAIT cells have varying capacities to produce effector cytokines when activated.
MAIT cells have transcriptional signatures associated with early effector function.
TCR-dependent activation can be enhanced by addition of the KDM6B cofactor α-KG.
Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells
PE-ICs cycle at a time scale of ∼1 h in murine FDCs.
The trade-off between Ag protection and B cell uptake impacts GCs.
An in-silico Ag cycling blockade terminated GC reactions.
Insulin Receptor–Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice
High-risk relatives of T1D have significantly more IR+ T cells than T1D or controls.
A new transgenic mouse has insulitis in the pancreas via IR on T cells, but not T1D.
Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease
Rilzabrutinib oral BTK inhibitor has long residence time and low systemic exposure.
Rilzabrutinib shows multiple mechanisms of adaptive and innate immune responses.
Preclinical data support clinical use of rilzabrutinib for immune-mediated diseases.
Skin insults abruptly induce LRG, which warrants the proinflammatory responses.
Lrg deficiency leads to mitigated psoriasiform lesions in model mice.
LRG exerts feed-forward/feedback effects on skin inflammation via the skin–liver axis.
CLINICAL AND HUMAN IMMUNOLOGY
Distribution of T cell subsets is altered in COVID-19 compared to healthy subjects.
Cytotoxic and Th1 cells are activated and proliferating in COVID-19.
Activated and proliferating Th1 cells negatively correlate with plasma IL-6.
A type 1–immune bias is more common in patients with IDH1R132H mutant than IDHwt AA.
AA progression is associated with a type 1 to type 2 shift in systemic immune bias.
Type 2–immune bias, tumor vascular leakage, and TAM levels indicate poor AA prognosis.
Influenza-specific memory B cells have accessible chromatin structure.
Human and mouse memory B cells upregulate heme metabolic pathways.
Heme enhances PC differentiation and augments mitochondrial metabolism ex vivo.
IKAROS ZF1 is crucial for normal development and function of B cells, but not T cells.
The L132P mutation in IKAROS confers a CVID-like phenotype in mice.
The Zinc Finger Protein Zbtb18 Represses Expression of Class I Phosphatidylinositol 3-Kinase Subunits and Inhibits Plasma Cell Differentiation
The Zinc finger protein, Zbtb18, is downregulated during PC differentiation.
Enhanced expression of Zbtb18 leads to impaired PC development.
Zbtb18 directly binds and inhibits expression of PI3K subunits.
TRIM28 Expression on Dendritic Cells Prevents Excessive T Cell Priming by Silencing Endogenous Retrovirus
DCs from old mice show decrease of TRIM28 transcription and phosphorylation.
TRIM28 loss on DCs augments T cell priming that exacerbates EAE reaction.
Dysregulated endogenous retroelements drive inflammatory gene expression.
Nrf2 regulates IL-22 responses in CD4+ T cells.
Nrf2 activation inhibits IL-17A response in multiple sclerosis patient–derived PBMCs.
IMMUNE SYSTEM DEVELOPMENT
Outside-in integrin signaling regulates splenic HSC proliferation and function.
Lack of POSTN–ITGAV interaction affects myofibroblasts in splenic trabecular area.
POSTN modulates splenic niche creation and supports splenic and incoming HSCs.
IMMUNOTHERAPY AND VACCINES
Toxicity risk can be identified early by tumor burden and fever characteristics.
Cytokine-based algorithms have excellent predictive power.
INFECTIOUS DISEASE AND HOST RESPONSE
IL-1 Receptor Antagonist Anakinra in the Treatment of COVID-19 Acute Respiratory Distress Syndrome: A Retrospective, Observational Study
Anakinra improved 28-day survival rate in patients with COVID-19–associated ARDS.
Anakinra was well tolerated, with no increase in infection-related adverse events.
The Butyrate-Producing Bacterium Clostridium butyricum Suppresses Clostridioides difficile Infection via Neutrophil- and Antimicrobial Cytokine–Dependent but GPR43/109a-Independent Mechanisms
Clostridium butyricum strain MIYAIRI588 (CBM588) protects mice from CDI.
CBM588 elicits neutrophil recruitment and Th1 and Th17 immunity in the gut.
The protective effects of CBM588 are independent of GPR43 and GPR109a.
IL-21/IL-21R Signaling Aggravated Respiratory Inflammation Induced by Intracellular Bacteria through Regulation of CD4+ T Cell Subset Responses
IL-21/IL-21R can aggravate C. muridarum lung infection.
IL-21/IL-21R can suppress Th1/Th17 cell responses in C. muridarum lung infection.
COVID-19 is associated with immune-inflammation dysregulation in blood and lung.
CEA, IL-8, and S100A8/A9 in serum were useful for differentiating COVID-19 from influenza.
IL-6, CEA, IL-8, S100A8/A9, and proteinase 3 in BALF are predictive of COVID-19 severity.
INNATE IMMUNITY AND INFLAMMATION
Extracellular rhERAPs trigger innate immunity.
Anti–HIV-1 activity of extracellular ERAPs relies on monocyte/macrophage activation.
Helminth Imprinting of Hematopoietic Stem Cells Sustains Anti-Inflammatory Trained Innate Immunity That Attenuates Autoimmune Disease
Helminth products imprint long-term hematopoietic stem cells.
Helminth-imprinted hematopoietic stem cells generate anti-inflammatory macrophages.
Helminths attenuate autoimmunity by promoting anti-inflammatory trained immunity.
Noncytotoxic Inhibition of the Immunoproteasome Regulates Human Immune Cells In Vitro and Suppresses Cutaneous Inflammation in the Mouse
The immunoproteasome controls the activation of immune cells.
An inhibitor of the immunoproteasome without cellular toxicity is described.
PKS3053 decreases inflammation and tissue damage in a moderate cutaneous injury model.
IFNs Reset the Differential Capacity of Human Monocyte Subsets to Produce IL-12 in Response to Microbial Stimulation
Human monocyte subsets have distinct IFN-γ priming requirements for IL-12 production.
IFN-γ boosts monocyte IL-12 response by priming the less responsive CD16neg subset.
IFN-α fails to enhance monocyte IL-12 production but inhibits their priming by IFN-γ.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
The Crystal Structure of the MHC Class I (MHC-I) Molecule in the Green Anole Lizard Demonstrates the Unique MHC-I System in Reptiles
The first atomic structure of the reptile pMHC-I reveals the unique MHC-I system.
The pMHC-I includes an unusual flip and an upward shift in the α1/α2–helical regions.
The peptide presentation motif and profile of the reptile pMHC-I were determined.
Functional Characteristics and Phenotypic Plasticity of CD57+PD1− CD4 T Cells and Their Relationship with Transplant Immunosuppression
CD57+PD1− CD4 T cells can proliferate when in the presence of unsorted PBMC.
Rapamycin increases expression of PD1 on stimulated CD57+PD1− CD4 T cells.
On the cover: The peptide binding groove of the reptile peptide–MHC class I–β2 microglobulin is mainly composed of the main anchor amino acids that form a hydrogen bond and salt bridge network that interacts with the peptide, and P9 (green) is deeply embedded in the strongly hydrophobic and positively charged F pocket. Wang, Y., Z. Qu, L. Ma, X. Wei, N. Zhang, B. Zhang, and C. Xia. 2021. The crystal structure of the MHC class I (MHC-I) molecule in the green anole lizard demonstrates the unique MHC-I system in reptiles. J. Immunol. 206: 1653–1667.
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