Immunology

Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies

Immunity - 20 March 2018 - 12:00am
Patel and Minn present a conceptual framework for the design of combination therapies wherein combination approaches are aimed at restoring discriminatory functions of the immune system that are corrupted by cancer—antigenicity, adjuvanticity, and feedback inhibition.
Categories: Immunology

Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction

Immunity - 20 March 2018 - 12:00am
Li et al. find that clonal expansion of high affinity B cells in GCs depends on the Cbl ubiquitin ligases, which prevent premature GC exit by promoting the degradation of Irf4 in light zone B cells. Strong CD40 and BCR signals trigger Cbl degradation, thus enabling GC exit.
Categories: Immunology

IL-33 Deals with the Gray Matter

Immunity - 20 March 2018 - 12:00am
The central nervous system undergoes extensive postnatal synapse remodeling that is critical for the formation of mature neural circuits. In a recent issue of Science, Vainchtein et al. (2018) describe an additional role for astrocyte-derived interleukin-33 (IL-33) in promoting synapse refinement by microglia in the developing brain.
Categories: Immunology

Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape

Immunity - 20 March 2018 - 12:00am
Wellenstein and de Visser review the mechanisms whereby drivers of tumorigenesis shape the tumor microenvironment and tumor immunity and place these findings in the context of clinical observations of responsiveness and resistance to immune checkpoint blockade therapies.
Categories: Immunology

Loss of NF-κB1 Causes Gastric Cancer with Aberrant Inflammation and Expression of Immune Checkpoint Regulators in a STAT-1-Dependent Manner

Immunity - 20 March 2018 - 12:00am
The links between NF-κB signaling, inflammation, and tumorigenesis are poorly understood. O’Reilly et al. reveal that NF-κB1 deficiency causes gastric cancer by dysregulating inflammation and immune checkpoints through a STAT1-dependent process. This may explain how polymorphisms in NFKB1 that impair its expression predispose to the development of epithelial cancers.
Categories: Immunology

Mitochondria-ER Pas de Deux Controls Memory T Cell Function

Immunity - 20 March 2018 - 12:00am
Memory CD8+ T cells mediate protective secondary immune responses. In this issue, Bantug et al. (2018) demonstrate that mTORC2-AKT-GSK3β signaling at mitochondria-ER contact sites enables the TCA cycle flux that is necessary for memory CD8+ T cells to produce IFN-γ.
Categories: Immunology

A Talented Duo: IFIT1 and IFIT3 Patrol Viral RNA Caps

Immunity - 20 March 2018 - 12:00am
Hosts respond to viral infection by expressing interferon-stimulated genes, of which IFITs are potent inhibitors of viral RNA translation. Johnson et al. (2018) solved the structure of the IFIT1-IFIT3 complex bound cap 0 RNA and explored their concerted antiviral activity.
Categories: Immunology

Is it dead or alive? TLR8 can tell

Nature Immunology - 19 March 2018 - 12:00am

Is it dead or alive? TLR8 can tell

Is it dead or alive? TLR8 can tell, Published online: 19 March 2018; doi:10.1038/s41590-018-0070-x

The sensing of viable pathogens by the receptor TLR8 on human monocytes provides key signals that initiate the differentiation of naive CD4+ T cells into follicular helper T cells. Targeting TLR8 might represent a novel approach for improving immunity following vaccination.
Categories: Immunology

Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33

Nature Immunology - 19 March 2018 - 12:00am

Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33

Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33, Published online: 19 March 2018; doi:10.1038/s41590-018-0067-5

The cytokine IL-33 has major roles in type 2 immunity and allergy. Girard and colleagues demonstrate that a broad range of allergens across multiple kingdoms can directly cleave IL-33 via their intrinsic protease activity and convert it into a highly active processed form.
Categories: Immunology

Recognition of microbial viability via TLR8 drives T<sub>FH</sub> cell differentiation and vaccine responses

Nature Immunology - 19 March 2018 - 12:00am

Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses

Recognition of microbial viability via TLR8 drives T<sub>FH</sub> cell differentiation and vaccine responses, Published online: 19 March 2018; doi:10.1038/s41590-018-0068-4

Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote TFH cell differentiation and vaccine responses through the induction of a specific cytokine profile.
Categories: Immunology

A tumor–myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer

Nature Immunology - 19 March 2018 - 12:00am

A tumor–myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer

A tumor–myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer, Published online: 19 March 2018; doi:10.1038/s41590-018-0066-6

Tumor cells commonly manipulate their environment to ensure their survival. Kuan and Ziegler show that breast cancer cells release IL-1α, which acts on infiltrating myeloid cells to elicit their production of TSLP. In turn, TSLP promotes the survival of TSLPR+ tumor cells by upregulating expression of the pro-survival factor Bcl-2.
Categories: Immunology

Lysine Deacetylases and Regulated Glycolysis in Macrophages

Trends Immunology - 19 March 2018 - 12:00am
Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes.
Categories: Immunology

Origin and Immunological Functions of Spleen Stromal Cells

Trends Immunology - 19 March 2018 - 12:00am
The mammalian spleen is a peripheral lymphoid organ that plays a central role in host defense. Consequently, the lack of spleen is often associated with immunodeficiency and increased risk of overwhelming infections. Growing evidence suggests that non-hematopoietic stromal cells are central players in spleen development, organization, and immune functions. In addition to its immunological role, the spleen also provides a site for extramedullary hematopoiesis (EMH) in response to injuries. A deeper understanding of the biology of stromal cells is therefore essential to fully comprehend how these cells modulate the immune system during normal and pathological conditions.
Categories: Immunology

Cutaneous Barriers and Skin Immunity: Differentiating A Connected Network

Trends Immunology - 15 March 2018 - 12:00am
The skin is the outermost barrier of the organism that ensures protection from external harm. Lately, our view of the skin has evolved from an inert mechanical barrier to an active organ that can sense danger signals and mount perfectly adapted defense measures in response to invading pathogens. This Review highlights the different levels of the cutaneous barrier (the microbiome, chemical, physical, and immune barriers), their characteristics, and functional, highly interconnected network of cells and mediators that allow balanced defense measures to protect the body and maintain barrier integrity.
Categories: Immunology

Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner

Immunity - 13 March 2018 - 12:00am
Little is known about the epigenetic signals that control microglia function in vivo. Datta et al. show that histone deacetylases Hdac1 and Hdac2 are essential for microglial survival and expansion during development but not during steady state. In Alzheimer’s disease mouse model, deletion of microglial Hdac1 and Hdac2 reduces amyloid pathology and improves cognitive function.
Categories: Immunology

Sensing Microbial Viability through Bacterial RNA Augments T Follicular Helper Cell and Antibody Responses

Immunity - 13 March 2018 - 12:00am
Live vaccines typically elicit augmented humoral responses, affording superior protection. Barbet et al. report that innate detection of bacterial RNA, a signature of microbial viability, directs a heightened Tfh cell response. This response is extrinsic to B cells and dendritic cells and involves CX3CR1+CCR2– monocyte instruction of Tfh differentiation via TRIF-dependent IFN-β licensing of bacterial RNA-driven inflammasome activation.
Categories: Immunology

A Neutralizing Antibody Recognizing Primarily N-linked Glycan Targets the Silent Face of the HIV Envelope

Immunity - 13 March 2018 - 12:00am
The center of the “silent face” on the HIV-1 envelope is shielded by glycans and has been devoid of antibody recognition. Zhou et al. identify the antibody VRC-PG05, which binds a glycan-dominated epitope at the silent face center and completes antibody recognition of all major exposed regions of the envelope trimer.
Categories: Immunology

T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids

Nature Immunology - 12 March 2018 - 12:00am

T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids

T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids, Published online: 12 March 2018; doi:10.1038/s41590-018-0065-7

CD1 molecules present diverse lipid ligands to TCRs expressed by NKT cells. Rossjohn, Moody and colleagues show a unique form of autoreactivity with human CD1c molecules, whereby TCRs recognize a closed conformation of CD1c molecules, which are loaded with a diverse array of ‘headless’ glycolipids.
Categories: Immunology

Immunology of Uterine and Vaginal Mucosae

Trends Immunology - 9 March 2018 - 12:00am
Due to errors that occurred during the preparation of the article, one of the author’s affiliations was incorrect. The affiliations for Sing Sing Way should be Division of Infectious Disease, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA and Perinatal Institute, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA. This has been corrected in the online version of the article and the correct version appears in print.
Categories: Immunology

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