Constitutive IL-6 overproduction promotes myeloid cell–driven inflammation.
IL-6Rα (CD126) is indispensable for IL-6–mediated STAT3 activation in mice.
ALLERGY AND OTHER HYPERSENSITIVITIES
Allergin-1 inhibits HDM-induced Syk activation via SHP-1 in CD11b+ DC.
Allergin-1 suppresses Th2 response by inhibiting Syk-mediated PGE2 production in DC.
Pyruvate Kinase M2 Promotes Expression of Proinflammatory Mediators in House Dust Mite–Induced Allergic Airways Disease
A small molecular activator of PKM2 attenuates allergic airways disease in mice.
Activation of PKM2 decreases IL-1β–induced airway inflammation.
PKM2 activation decreases IL-1β–induced nuclear phosphorylation of STAT3.
ANTIGEN RECOGNITION AND RESPONSES
Immunodominant AH1 Antigen-Deficient Necroptotic, but Not Apoptotic, Murine Cancer Cells Induce Antitumor Protection
ICD of CT26 cells relies mainly on AH1 tumor Ag expression.
AH1-deficient necroptosis remains more immunogenic compared with apoptosis.
Necroptotic, but not apoptotic, CT26 cells generate immunity against neoepitopes.
The VR23 Antitumor Compound Also Shows Strong Anti-Inflammatory Effects in a Human Rheumatoid Arthritis Cell Model and Acute Lung Inflammation in Mice
Anticancer VR23 also effectively downregulates inflammatory cytokines in monocytes.
VR23 effectively downregulates MCP-1, IL-6, and cell migration in human synoviocytes.
VR23 effectively downregulates lung inflammation caused by LPS in mice.
Type II but Not Type I IFN Signaling Is Indispensable for TLR7-Promoted Development of Autoreactive B Cells and Systemic Autoimmunity
IFN-γ but not type I IFN signaling is indispensable for TLR7-driven autoimmunity.
IFN-γ promotes TLR7-accelerated SLE by regulating multiple cellular pathways.
IFN-γ signaling in B cells is required for development of TLR7-accelerated SLE.
IMP761 is a humanized IgG4 LAG-3–specific Ab with agonistic properties.
IMP761 is immunosuppressive in vitro and in vivo.
Targeting LAG-3 represents a promising novel therapeutic approach for treating AID.
CLINICAL AND HUMAN IMMUNOLOGY
IL-3 Receptor Expression on Activated Human Th Cells Is Regulated by IL-4, and IL-3 Synergizes with IL-4 to Enhance Th2 Cell Differentiation
Activated human Th cells show IL-3R surface expression, which is increased by IL-4.
IL-3R+ cells show a Th2 phenotype, and their effector functions are enhanced by IL-3.
A higher number of IL-3– and IL-3R–expressing Th cells were seen in allergic patients.
Functional Variation of IL-1R–Associated Kinases in the Conserved MyD88–TRAF6 Pathway during Evolution
Amphioxus has IRAK4 and Pelle; Pelle was displaced by IRAK1/2/3 in vertebrates.
IRAK4 and Pelle show different function in amphioxus, vertebrates, and Drosophila.
IRAKs may confer plasticity to the evolution of the TLR/IL-1R pathways.
IL-7R–Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis
PI3K competes with STAT5 in IL-7R signaling and maintains an appropriate signal balance.
Early and memory T cell development is modulated by a competition between IL-7R signals.
A competition in IL-7R signaling modulates the population size of peripheral T cells.
IMMUNE SYSTEM DEVELOPMENT
TCR Repertoires of Thymic Conventional and Regulatory T Cells: Identification and Characterization of Both Unique and Shared TCR Sequences
αβ TCR sequences of tTreg and Tconv are distinguished by an ML algorithm.
A fraction of αβ TCR sequences of tTreg and Tconv are conserved across mice.
Osteoclasts Derive Predominantly from Bone Marrow–Resident CX3CR1+ Precursor Cells in Homeostasis, whereas Circulating CX3CR1+ Cells Contribute to Osteoclast Development during Fracture Repair
OCP express CX3CR1 and, in unperturbed conditions, differentiate into osteoclasts.
The contribution of circulating CX3CR1+ OCP to OC development is low during homeostasis.
Mature OC can originate from circulating CX3CR1+ cells during fracture repair.
Neuroimmune/Hematopoietic Axis with Distinct Regulation by the High-Mobility Group Box 1 in Association with Tachykinin Peptides
SP induces the HMGB1 gene in BM stroma.
NK-A, via HMGB1, negatively regulates SP effects on hematopoiesis.
Humanized mice confirmed HMGB1 exerting negative hematopoietic effects.
A new, MHC-linked class I gene (UDA) was found in cartilaginous fishes.
UDA is monomorphic and in single/low copy number in elasmobranchs.
Chondrichtyans have at least four class I lineages, one classical and three nonclassical.
IMMUNOTHERAPY AND VACCINES
Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non–Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae
Bicistronic Ag–molecular adjuvant vectors induce distinct immune profiles.
CCL20 and CCL28 induce homing of Ag-specific T cells to the female genital tract.
CCL20 and CCL25 induce homing of Ag-specific B cells to the intestinal mucosa.
Magnitude and Functional Profile of the Human CD4+ T Cell Response throughout Primary Immunization with Tick-Borne Encephalitis Virus Vaccine
Primary TBE immunization induces heterogenous magnitude of CD4+ T cell response.
The response is marked by IL-2, TNF, and CD154 expression after each vaccine dose.
IFN-γ response by memory CD4+ T cells in TBE vaccinees is lower than in TBE patients.
INFECTIOUS DISEASE AND HOST RESPONSE
BHLHE40 Promotes TH2 Cell–Mediated Antihelminth Immunity and Reveals Cooperative CSF2RB Family Cytokines
BHLHE40 is required for protective immunity to the helminth H. polygyrus.
BHLHE40 is required for normal TH2 gene transcription and cytokine production.
CSF2RB-dependent cytokines can compensate for each other during type 2 immunity.
Vinpocetine suppresses S. pneumoniae–induced inflammation in vitro and in vivo.
Vinpocetine inhibits S. pneumoniae–induced inflammation via upregulating CYLD.
CYLD suppresses S. pneumoniae–induced inflammation via inhibiting ERK.
The genetic variation in the proximal promoter region alters MHCII expression.
Lower MHCII-DRB expression leads to poor parasite clearance.
MHCII gene regulation determines the immunity to malaria.
INNATE IMMUNITY AND INFLAMMATION
Neutrophils express LILRB3, which is released in a soluble form upon activation.
LILRB3 inhibits FcαR-mediated neutrophil activation and effector functions.
Intracellular IL-1 Receptor Antagonist Isoform 1 Released from Keratinocytes upon Cell Death Acts as an Inhibitor for the Alarmin IL-1α
Deficiency in icIL-1Ra1 aggravates psoriasis-like skin inflammation in mice.
icIL-1Ra1 is released from keratinocytes during lytic cell death.
icIL-1Ra1 counteracts the inflammatory effects of the alarmin IL-1α.
NI in the colon affects barrier function later in life.
NI sensitizes the Mir155 promoter for aberrant epigenetic activation.
miR-155 suppresses E-cadherin protein expression in the colonic epithelium.
Therapeutic Targeting of Vasculature in the Premetastatic and Metastatic Niches Reduces Lung Metastasis
Angiogenesis contributes to the lung premetastatic niche in a model of breast cancer.
This angiogenesis is initiated by C5a/C5aR1-regulated MDSC.
Inhibition of C5aR1 combined with antiangiogenic vaccines reduces lung metastasis.
IL-33 treatment upregulated PGD2 synthesis genes.
IL-33–elicited lung ILC2 accumulation was partially dependent on the PGD2 receptor CRTH2.
CRTH2 controlled IL-33–elicited ILC2 lung accumulation via migration/tissue retention.
ARF6 regulates the polarization of RPH3A and RAB21 at the plasma membrane.
ARF6 binds to RPH3A and augments the interaction between plasma membrane PtdIns4P and RPH3A.
ARF6 is important for neutrophil adhesion on the inflamed endothelia.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Choice of Host Cell Line Is Essential for the Functional Glycosylation of the Fc Region of Human IgG1 Inhibitors of Influenza B Viruses
Choice of cell line is critical for functional glycosylation of human IgG1-Fc.
Sialylated IgG1-Fc monomers block influenza B only when made by CHO-K1 cells.
Polysaccharide Capsules Equip the Human Symbiont Bacteroides thetaiotaomicron to Modulate Immune Responses to a Dominant Antigen in the Intestine
B. thetaiotaomicron CPSs control the activation of T cells and the clearance of Ag in vivo.
Antistimulatory CPSs activate innate immunity weaker than prostimulatory CPSs.
Antistimulatory CPSs block APC access, which can be rescued by opsonization.
IRF4-expressing cDC2 promote early T cell–dependent colitis.
IRF4-expressing cDC2 promote the generation of colitogenic CD4+ T cells.
IRF4-expressing cDC2 are not required for Treg-mediated suppression of colitis.
Mast Cells Localize in Hypoxic Zones of Tumors and Secrete CCL-2 under Hypoxia through Activation of L-Type Calcium Channels
MCs are mainly located in hypoxic zones of murine melanoma tumors.
Hypoxia induces CCL-2 production via ROS generation and LVDCCs activation.
Hypoxia promotes glutathionylation and membrane translocation of LVDCCs in BMMCs.
Correction: Soluble B and T Lymphocyte Attenuator Possesses Antitumor Effects and Facilitates Heat Shock Protein 70 Vaccine-Triggered Antitumor Immunity against a Murine TC-1 Cervical Cancer Model In Vivo
On the cover: The human gut symbiont Bacteroides thetaiotaomicron expresses one of eight capsular polysaccharides in a phase-variable manner. The individual capsules have a range of effects on the CD4+ T cell response to B. thetaiotaomicron—from antistimulatory to prostimulatory. The capsule is shown in yellow in a quick-freeze, deep-etch scanning electron micrograph. Hsieh, S., N. T. Porter, D. L. Donermeyer, S. Horvath, G. Strout, B. T. Saunders, N. Zhang, B. Zinselmeyer, E. C. Martens, T. S. Stappenbeck, and P. M. Allen. 2020. Polysaccharide capsules equip the human symbiont Bacteroides thetaiotaomicron to modulate immune responses to a dominant antigen in the intestine. J. Immunol. 204: 1035–1046.
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