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Trends in Immunology

Michelle L McCully, Ariadni Kouzeli, Bernhard Moser
Cellular immunity is governed by a complex network of migratory cues that enable appropriate immune cell responses in a timely and spatially controlled fashion. This review focuses on the chemokines and their receptors regulating the steady-state localisation of immune cells within healthy peripheral tissues. Steady-state immune cell traffic is not well understood but is thought to involve constitutive (homeostatic) chemokines. The recent discovery of tissue-resident memory T cells (TRM cells) illustrates our need for understanding how chemokines control immune cell mobilisation and/or retention...
July 9, 2018: Trends in Immunology
María E Rodríguez-Ruiz, Claire Vanpouille-Box, Ignacio Melero, Silvia Chiara Formenti, Sandra Demaria
Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy...
July 9, 2018: Trends in Immunology
Angela R M Kurz, Sergio D Catz, Markus Sperandio
The mammalian sterile 20-like (MST) kinases are central constituents of the evolutionary ancient canonical Hippo pathway regulating cell proliferation and survival. However, perhaps surprisingly, MST1 deficiency in human patients leads to a severe combined immunodeficiency syndrome with features of autoimmune disease. In line with this, Mst1-deficient mice exhibit severe defects in lymphocyte and neutrophil functions as well as disturbed intracellular vesicle transport. These findings spurred research on the noncanonical functions of MST1 in leukocytes...
June 25, 2018: Trends in Immunology
Alexis Rapin, Nicola L Harris
Intestinal helminths, along with mutualistic microbes, have cohabited the intestine of mammals throughout evolution. Interactions between helminths, bacteria, and their mammalian hosts may shape not only host-helminth and host-microbiome interactions, but also the relationship between helminths and the microbiome. This 'ménage à trois' situation may not be completely balanced in that it may favor either the host or the parasite, possibly at the cost of the other partner. Similarly, helminths may favor the establishment of a particular microbiome with either positive or negative consequences for the overall health and well-being of the host...
June 22, 2018: Trends in Immunology
Olga Moreno-Gonzalo, Federico Mayor, Francisco Sánchez-Madrid
Histone deacetylase 6 (HDAC6) acts by enzyme-dependent and -independent mechanisms to regulate diverse cellular processes including autophagy, the ubiquitin proteasome system, and cell migration. HDAC6 also has emerging roles in innate immunity, including pathogen sensing and destruction, thus placing this enzyme at the crossroads of infection and innate immunity.
June 21, 2018: Trends in Immunology
Timon E Adolph, Christoph Grander, Alexander R Moschen, Herbert Tilg
The intestinal and hepatobiliary tract exhibits host-specific commensal colonization. The resident microbiota has emerged as a key player in intestinal and hepatic diseases. Alcoholic and nonalcoholic fatty liver diseases (ALD/NAFLD), primary sclerosing cholangitis (PSC), liver cirrhosis, and some of their clinical complications, such as hepatic encephalopathy (HE), have been linked to a microbial signature, as also observed for severe liver inflammation in alcoholic hepatitis. In turn, the liver impacts, and communicates with, the microbiota through hepatic mediators, such as bile acids or inflammatory signals...
May 26, 2018: Trends in Immunology
Tae Kon Kim, Roy S Herbst, Lieping Chen
Despite the unprecedented tumor regression and long-term survival benefit observed with anti-programmed death (PD) [anti-PD-1 or anti-B7-homolog 1 (B7-H1)] therapy in patients with advanced cancers, a large portion of patients do not benefit from such treatment and a fraction of responders relapse. Current efforts to overcome resistance and improve efficacy of anti-PD therapy require a clear understanding of resistance and should precede current avenues using random combinations with available treatment regimens...
May 22, 2018: Trends in Immunology
Hélène D Moreau, Matthieu Piel, Raphaël Voituriez, Ana-Maria Lennon-Duménil
The function of most immune cells depends on their ability to migrate through complex microenvironments, either randomly to patrol for the presence of antigens or directionally to reach their next site of action. The actin cytoskeleton and its partners are key conductors of immune cell migration as they control the intrinsic migratory properties of leukocytes as well as their capacity to respond to cues present in their environment. In this review we focus on the latest discoveries regarding the role of the actomyosin cytoskeleton in optimizing immune cell migration in complex environments, with a special focus on recent insights provided by physical modeling...
May 17, 2018: Trends in Immunology
Ivan Budnik, Alexander Brill
Deep vein thrombosis (DVT) is a major origin of morbidity and mortality. While DVT has long been considered as blood coagulation disorder, several recent lines of evidence demonstrate that immune cells and inflammatory processes are involved in DVT initiation. Here, we discuss these mechanisms, in particular, the role of immune cells in endothelial activation, and the immune cascades leading to expression of adhesion receptors on endothelial cells. We analyze the specific recruitment and functional roles of different immune cells, such as mast cells and leukocytes, in DVT...
May 15, 2018: Trends in Immunology
Juan Rivera-Correa, Ana Rodriguez
Antiself antibodies are most commonly associated with autoimmune disorders, but a large body of evidence indicates that they are also present in numerous infectious diseases. These autoimmune antibodies appear transiently during infection with a number of viruses, bacteria, and parasites and in some cases have been associated with the development of autoimmune disorders that develop after infection has been cleared. Traditionally these infection-associated autoantibodies are considered an erroneous byproduct of a legitimate immune response, but their possible role in the clearance of microbes and infected cells or inhibition of host-cell invasion suggests that they may be present because of their beneficial protective role against various infections...
April 30, 2018: Trends in Immunology
Joannie M Allaire, Shauna M Crowley, Hong T Law, Sun-Young Chang, Hyun-Jeong Ko, Bruce A Vallance
The gastrointestinal (GI) tract represents a unique challenge to the mammalian immune system. It must tolerate the presence of the luminal microbiota and thus not respond to their products, but still protect the intestinal mucosa from potentially harmful dietary antigens and invading pathogens. The intestinal epithelium, composed of a single layer of cells, is crucial for preserving gut homeostasis and acts both as a physical barrier and as a coordinating hub for immune defense and crosstalk between bacteria and immune cells...
April 28, 2018: Trends in Immunology
Franco Locatelli, Daniela Pende, Michela Falco, Mariella Della Chiesa, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells are involved in innate defenses against viruses and tumors. Their function is finely tuned by activating and inhibitory receptors. Among the latter, killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This latter phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor...
July 2018: Trends in Immunology
Davide Angeletti, Jonathan W Yewdell
Adaptive immune responses against antigenically variable viruses and cellular pathogens are efficient in many cases, but largely limited to the infecting or immunizing strain. A major factor that limits immunity is immunodominance (ID), the hierarchical focusing of adaptive immune responses on a subset of antigenic determinants. While CD8+ T cell ID has been extensively studied, studies of basic mechanisms of B cell ID are limited, despite the importance of antibodies (Abs) for durable protection against pathogens...
July 2018: Trends in Immunology
Julie Y Zhou, Douglas M Oswald, Kelsey D Oliva, Lori S C Kreisman, Brian A Cobb
Carbohydrates, or glycans, are as integral to biology as nucleic acids and proteins. In immunology, glycans are well known to drive diverse functions ranging from glycosaminoglycan-mediated chemokine presentation and selectin-dependent leukocyte trafficking to the discrimination of self and non-self through the recognition of sialic acids by Siglec (sialic acid-binding Ig-like lectin) receptors. In recent years, a number of key immunological discoveries are driving a renewed and burgeoning appreciation for the importance of glycans...
July 2018: Trends in Immunology
Chung-Han Lee, Roman Yelensky, Karin Jooss, Timothy A Chan
Antitumor rejection by the immune system is a complex process that is regulated by several factors. Among these factors are the quality and quantity of mutational events that occur in cancer cells. Perhaps one of the most important types of mutations that influence antitumor immunity is the neoantigen, that is, a non-self-antigen that arises as a result of somatic mutation. Recent work has demonstrated that neoantigens hold significant promise for developing new diagnostic and therapeutic modalities. Therapeutic targeting of neoantigens is important for achieving benefit following therapy with immune checkpoint blockade agents or for cancer vaccines targeting mutations...
July 2018: Trends in Immunology
Nick Huang, Andras Perl
Metabolic pathways are now well recognized as important regulators of immune differentiation and activation, and thus influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanistic target of rapamycin (mTOR) has emerged as a key sensor of metabolic stress and an important mediator of proinflammatory lineage specification. Metabolic pathways control the production of mitochondrial reactive oxygen species (ROS), which promote mTOR activation and also modulate the antigenicity of proteins, lipids, and DNA, thus placing ROS at the heart of metabolic disturbances during pathogenesis of SLE...
July 2018: Trends in Immunology
Michael Bauer, Sebastian Weis, Mihai G Netea, Reinhard Wetzker
Recent investigations reveal memory-like adaptive responses of the innate immune system to sequential pathogen challenge. Of note, opposing effects that include both sensitization ('training') and desensitization ('tolerance') have been reported. While hitherto the nature of the pathogen was thought to be of prime importance, we propose that pathogen dose plays a key role in determining these opposing effects. Within this concept, training and tolerance of innate immune cells emerge as adaptive responses to increasing pathogen load...
June 2018: Trends in Immunology
Martin S Davey, Carrie R Willcox, Alfie T Baker, Stuart Hunter, Benjamin E Willcox
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...
June 2018: Trends in Immunology
Claire Vanpouille-Box, Silvia C Formenti
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.
June 2018: Trends in Immunology
Rachel Golub, Jonathan Tan, Takeshi Watanabe, Andrea Brendolan
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...
June 2018: Trends in Immunology
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