Immunology

Visualizing TGF-β1 regulation by GARP
Regulatory T cells (Tregs) can suppress immune responses through a variety of mechanisms. One such mechanism involves the activation of a surface-bound latent form of the cytokine transforming growth factor–β1 (TGF-β1). Within the cell, newly synthesized pro-TGF-β1 homodimers form disulfide bonds with the transmembrane protein GARP, which acts to chaperone and orient the cytokine for activation at the cell surface. Liénart et al. reveal how GARP interacts with TGF-β1, using a crystal structure in which the complex was stabilized using a Fab fragment from a monoclonal antibody (MHG-8) that binds to the complex. In so doing, they also demonstrate how MHG-8 prevents membrane-associated TGF-β1 release. These structural and mechanistic insights may inform treatments of diseases with altered TGF-β1 functionality and dysfunctional Treg activity, including cancer immunotherapy.

Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying
six immune subtypes that encompass multiple cancer types and are hypothesized to define
immune response patterns impacting prognosis.

Caltech scientists have now identified the complex role a particular protein plays in helping stem cells develop into T-lymphocytes, powerful immune cells.

Genome Med. 2018 May 25;10(1):39. doi: 10.1186/s13073-018-0553-2. Research Support, Non-U.S.Gov't; Review...

About HIPC The Human Immunology Project Consortium (HIPC) program was established in 2010, and renewed in 2015, by the NIAID Division of Allergy, Immunology, and Transplantation as part of the overall NIAID focus on human immunology. Through this program, well-characterized human cohorts are studied using a variety of modern analytic tools, including multiplex transcriptional, cytokine, and proteomic assays; multiparameter phenotyping of leukocyte subsets; assessment of leukocyte functional status; and multiple computational methods. Read more »

05 December 2018 12:00 p.m. ET Register now! Speakers Petter Brodin, M.D., Ph.D. Karolinska Institute  Stockholm, Sweden Yueh-hsiu Chien, Ph.D. Stanford University  Stanford, CA Moderated by Sean Sanders, Ph.D. Science/AAAS Washington, DC Sponsored by Olink Proteomics Immune systems are found in most living organisms. They reflect the common challenges of existing in a potentially hostile external environment, and often exhibit a complex, ever-changing interplay between specialized cell types, potent effector molecules, and exogenously acquired molecules and organisms. In our own immune systems, changes in the delicate homeostatic balance can lead to major problems, such as allergic responses or autoimmune diseases. Understanding how our immune system functions is difficult because of the plethora of different cell types and biomolecules involved, and because of its extremely dynamic nature. It is in constant coevolution with pathogens and must respond rapidly and specifically in each individual to a vast array of potential threats. Two major limitations of human immune system studies are their reliance on relatively few targeted assays and their potentially limited diversity within the samples examined. Studies that can provide genuine answers for immunological questions may require a systems biology approach that examines large numbers of different cell types and their interplay with real-time effector biomolecules, preferably using diverse sample cohorts. This webinar will focus on two such breakthrough studies (published in the journals Cell and Nature, respectively), which employ a broad, systems biology approach to better understand early postnatal immune system development, and the immunological control of latent infections. During the webinar, the speakers will: Describe how combining approaches such as mass cytometry, protein biomarker discovery, and transcriptomics provides valuable insights into complex immunological systems Reveal how the immune system develops in newborn children, and the external factors that influence this process Offer new insights into the complex pathophysiology of latent infections with Mycobacterium tuberculosis, using a multi-omic, multicohort approach Answer your questions during the live broadcast! This webinar will last for approximately 60 minutes. Speaker bios Petter Brodin, M.D., Ph.D. Karolinska Institute  Stockholm, Sweden Dr. Brodin is a pediatrician at the Karolinska University Hospital and an associate professor of immunology at the Karolinska Institute, both located in Stockholm, Sweden. He is also director of the National Mass Cytometry Facility at Sweden’s Science for Life Laboratory. He performed postdoctoral training with Mark Davis at the Stanford University School of Medicine (2012–2013) and developed an interest in the use of systems-level analyses as a means to advance human immunology. The Brodin lab now investigates human immune system variation, the factors that underlie this variation, and particularly how the external environment shapes our immune system in early life. The lab is also developing methods for systems-level profiling of immune function in various patient groups in order to improve clinical decision-making and outcomes. Yueh-hsiu Chien, Ph.D. Stanford University  Stanford, CA Dr. Chien is a professor in the Department of Microbiology and Immunology and in the immunology program at Stanford University. The question of how gamma-delta (γδ) T cells contribute to host immune defense has been the focus of her research group since soon after these cells were discovered. They have made several landmark discoveries, including isolating the T-cell receptor δ gene and showing that γδ T cells and αβ T cells are distinct in their antigen recognition and activation requirements, and also in their antigen-specific repertoire and effector-function development. These aspects allow γδ T cells to occupy unique temporal and functional niches to initiate and regulate the inflammatory response. More recently, Chien’s group also started to analyze the human immune system using systems biology approaches, such as exploring the effects of tuberculosis on the immune system. Dr. Chien holds a B.S. in chemistry from National Taiwan University and a Ph.D. in chemistry from the University of Illinois at Urbana-Champaign. She did her postdoctoral training at the California Institute of Technology.   Sean Sanders, Ph.D. Science/AAAS Washington, DC Dr. Sanders did his undergraduate training at the University of Cape Town, South Africa, and his Ph.D. at the University of Cambridge, UK, supported by the Wellcome Trust. Following postdoctoral training at the National Institutes of Health and Georgetown University, Dr. Sanders joined TranXenoGen, a startup biotechnology company in Massachusetts working on avian transgenics. Pursuing his parallel passion for writing and editing, Dr. Sanders joined BioTechniques as an editor, before joining Science/AAAS in 2006. Currently Dr. Sanders is the Senior Editor for Custom Publishing for the journal Science and Program Director for Outreach. Sponsored by

J Vet Med Sci. 2018 Nov 5. doi: 10.1292/jvms.18-0601.[Epub ahead of print]...

Lymph node tuberculosis (LNTB) is the most frequent extrapulmonary form of tuberculosis (TB). Studies of human tuberculosis at sites of disease are limited. LNTB provides a unique opportunity to compare local in situ and peripheral blood immune response in active Mycobacterium tuberculosis (Mtb)...

Review Article...

Human leukocyte antigens (HLA) are multi-allelic and polymorphic genes that present antigens to immune cells for inducing protective immunity. Here, using systems biology and structural approaches, the authors show that micropolymorphism of three HLA has effects beyond the modulation of antigen...