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Recasting Human Vδ1 Lymphocytes in an Adaptive Role

18 April 2018 - 12:00am
γδ T cells are unconventional lymphocytes commonly described as ‘innate-like’ in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges.
Categories: Immunology

Antibiotics as Instigators of Microbial Dysbiosis: Implications for Asthma and Allergy

11 April 2018 - 12:00am
The human body and its resident microbiota form a complex ecosystem, shaped by both inherited and environmental factors. The use of antibiotics represents an extreme example of environmental pressure and can broadly disrupt the microbial landscape. The benefits that antibiotics have brought to modern medicine are unquestionable; however, their overuse comes with consequences, including the potential for secondary infections by opportunistic pathogens and the spread of antibiotic resistance. Here, we discuss the implications of microbial dysbiosis driven by antibiotics, with a focus on potential links with allergy and asthma.
Categories: Immunology

Editorial Board and Contents

1 April 2018 - 12:00am
Categories: Immunology

Dual Transforming Growth Factor-β and Programmed Death-1 Blockade: A Strategy for Immune-Excluded Tumors?

26 March 2018 - 12:00am
Tumors that elude infiltration by CD8+ T lymphocytes are particularly resistant to multiple forms of treatment, including immune checkpoint blockade. Stromal transforming growth factor (TGF)-β appears to play a key role in this process, potentially constituting a target for novel combinatorial regimens tackling immune-excluded neoplasms.
Categories: Immunology

Carmen Gerlach

22 March 2018 - 12:00am
Due to an error in the preparation of this interview, the word ribosome was used mistakenly in the first section, where polymerase should have been employed. This error has been corrected and the relevant section now reads:
Categories: Immunology

The Impact of Sex on Alloimmunity

22 March 2018 - 12:00am
Transplantation outcomes are known to be affected by multiple factors, including donor and recipient sex. Aside from the physiological characteristics of male and female donor allografts, accumulating evidence suggests that additional features underlie sex-specific immune responses that affect graft survival. We discuss here aspects of innate and adaptive alloimmunity that are specific to males and females in the context of underlying genetic and hormonal factors. These differences likely contribute to the observed disparities in graft survival.
Categories: Immunology

Lysine Deacetylases and Regulated Glycolysis in Macrophages

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

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

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

Immunology of Uterine and Vaginal Mucosae

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

Innate Antiviral Immunity in the Skin

8 March 2018 - 12:00am
Barrier sites such as the skin play a critical role in immune defense. They must maintain homeostasis with commensals and rapidly detect and limit pathogen invasion. This is accomplished in part through the production of endogenous antimicrobial peptides and proteins, which can be either constitutive or inducible. Here, we focus particularly on the control of innate antiviral proteins and present the basic aspects of their regulation in the skin by interferons (IFNs), IFN-independent immunity, and environmental factors.
Categories: Immunology

To Each his Own

6 March 2018 - 12:00am
The now classical experiments reported by Medawar in the middle of the last century established the concept of an immune privilege for some sites: a transplant in the brain or eye of an autologous recipient could survive rejection, while the same tissue transplanted subcutaneously was swiftly rejected. These results suggested that the brain and the eye were somehow exempt from surveillance by immune cells. More broadly, these experiments hinted at the fact that, despite the existence of a circulating and supposedly autonomous immune system, local conditions mattered.
Categories: Immunology

What Can Immunologists Learn from Systems Approaches?

1 March 2018 - 12:00am
The field of systems immunology has grown extensively over the past few years, spurred by the generation of large data sets, and new analytical tools and modeling approaches. In this piece and its counterpart in Cell Systems (​http://www.cell.com/cell-systems/home), eight authors discuss what immunologists can learn from systems biology and, conversely, how systems biologists can use immune cells as a model, and outline the many directions in which this interdisciplinary field can expand.
Categories: Immunology

Editorial Board and Contents

1 March 2018 - 12:00am
Categories: Immunology

Immunomodulation as Rescue for Chronic Atonic Skin Wounds

27 February 2018 - 12:00am
Chronic skin wounds, caused by arterial or venous insufficiency or by physical pressure, constitute an increasing medical problem as populations age. Whereas typical wounds are characterized by local inflammation that participates in the healing process, atonic wounds lack inflammatory markers, such as neutrophil infiltration, and generally do not heal. Recently, prominent roles in the immunopathology of chronic wounds were attributed to dysregulations in specific cytokines, chemokines, matrix metalloproteinases (MMPs), and their substrates.
Categories: Immunology

Revisiting the Functional Impact of NK Cells

26 February 2018 - 12:00am
Immune responses are critical for the maintenance of homeostasis but can also upset the equilibrium, depending on the context and magnitude of the response. Natural killer (NK) cells are well known for their important roles in antiviral and antitumor immune responses, and they are currently used, mostly under optimized forms, as immunotherapeutic agents against cancer. Nevertheless, with accumulating examples of deleterious effects of NK cells, it is paramount to consider their negative contributions.
Categories: Immunology

Natural Killer Cells Detect a Tumor-Produced Growth Factor: A Vestige of Antiviral Resistance?

22 February 2018 - 12:00am
In addition to exogenous ligands derived from pathogens, natural killer (NK) and other innate cells can recognize endogenous ligands that often act as markers of stress or damage. A recent study reports that one of these receptors, human NKp44, recognizes PDGF-DD, providing a rare example of the recognition of a soluble growth factor as a stress signal. The recognition of PDGF-DD induces the secretion of cytokines with antitumor activity.
Categories: Immunology

Skin Commensal Antigens: Taking the Road Less Traveled

22 February 2018 - 12:00am
Although our knowledge of host–commensal interactions has increased exponentially, the mechanisms linking a specific commensal, its detection by the immune system, and its impact on tissue function are still often poorly understood. In a recent study in Cell, Linehan et al. dissect one of these interactions in the context of the skin, and demonstrate that Staphylococcus epidermidis antigens, presented through a non-classical pathway, drive the accumulation of CD8+ T cells that promote wound healing.
Categories: Immunology

Lipid Droplets as Immune Modulators in Myeloid Cells

22 February 2018 - 12:00am
Lipid droplets (LDs) were initially described as fat storage organelles in adipocytes, but are increasingly recognized as dynamic players in lipid metabolism, with important roles not only in diseases such as diabetes and cancer, but also in immune regulation. Alterations in immune cell function, such as myeloid cell activation, are connected to profound changes in LD numbers and LD protein composition. Thus, these organelles appear to be essential to metabolically support immune responses, and have a vital role in antigen crosspresentation, interferon (IFN) responses, production of inflammatory mediators, and pathogen clearance.
Categories: Immunology

Orchestration of NLRP3 Inflammasome Activation by Ion Fluxes

13 February 2018 - 12:00am
The assembly of the NLRP3 inflammasome can promote the release of IL-1β/IL-18 and initiate pyroptosis. Accordingly, the dysregulation of NLRP3 inflammasome activation is involved in a variety of human diseases, including gout, diabetes, and Alzheimer’s disease. NLRP3 can sense a variety of structurally unrelated pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to trigger inflammation, but the unifying mechanism of NLRP3 activation is still poorly understood.
Categories: Immunology

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