Table of contents


cover image
Top

Focus

Focus on inflammatory disease

There is an emerging understanding of how the disruption of immune homeostasis may lead to the development of chronic inflammatory diseases. This series of Reviews highlights new data that point toward the influence of environmental factors and addresses recent advances in our knowledge of the cell types and signaling pathways involved in inflammatory disease onset and progression.

Top

News

All aboard: Will molecular tumor boards help cancer patients? pp655 - 656

Jeanne Erdmann

doi:10.1038/nm0715-655


Almighty antibodies? A new wave of antibody-based approaches aims to combat HIV pp657 - 659

Erika Check Hayden

doi:10.1038/nm0715-657


Biomedical briefing pp660 - 661

doi:10.1038/nm0715-660


To build better tuberculosis diagnostics, look for 'biosignatures' p662

Alan Dove

doi:10.1038/nm0715-662


Top

News and Views

Liquid biopsies reveal the dynamic nature of resistance mechanisms in solid tumors pp663 - 665

Catherine B Meador & Christine M Lovly

doi:10.1038/nm.3899

Two new studies demonstrate that so-called 'liquid biopsies' may reveal important genomic information needed to monitor treatment responses, forecast tumor recurrences, and provide a rationale for novel therapeutic strategies in patients with lung cancer and colon cancer.

See also: Letter by Siravegna et al.


Shifts in macrophage cytokine production drive muscle fibrosis pp665 - 666

James G Tidball & Michelle Wehling-Henricks

doi:10.1038/nm.3896

Muscle fibrosis after acute injury can be debilitating, but in chronic muscle disease it can be lethal. A new study reveals that shifts in macrophage phenotype in injured or diseased muscle can influence whether connective tissue production by fibro/adipogenic precursors in muscle is beneficial or pathological.

See also: Article by Lemos et al.


Tracing human brown fat pp667 - 668

Mariëtte R Boon, Emmani B M Nascimento & Wouter D van Marken Lichtenbelt

doi:10.1038/nm.3900

Adipocyte progenitors have the capacity to differentiate into mature brown adipocytes with thermogenic capabilities. Two new studies identify novel markers to help prospectively isolate these and mature adipocytes from human brown fat biopsies.

See also: Article by Xue et al.


Top

Editorial

Focus on Inflammatory disease

Big data meets mechanism p673

doi:10.1038/nm.3903

Inflammatory disease research is burgeoning. Large data sets are being generated to characterize the human immune response, while detailed mechanistic studies are defining the role of specific cell types and sensors in inflammatory disease. Future efforts are needed to integrate these approaches and guide precision medicine.


Top

News

Focus on Inflammatory disease

A gut feeling about immunity pp674 - 676

Roxanne Khamsi

doi:10.1038/nm.3906

As it becomes evident that the microbiome exerts an influence on the human immune system, scientists have begun to ponder therapies that might act on intestinal microbes to reduce harmful inflammation. Roxanne Khamsi reports.


Top

Reviews

Focus on Inflammatory disease

Inflammasomes: mechanism of action, role in disease, and therapeutics pp677 - 687

Haitao Guo, Justin B Callaway & Jenny P-Y Ting

doi:10.1038/nm.3893


Focus on Inflammatory disease

The emerging role of resident memory T cells in protective immunity and inflammatory disease pp688 - 697

Chang Ook Park & Thomas S Kupper

doi:10.1038/nm.3883

Tissue-resident memory T cells are increasingly being linked to human tissue-specific immune and inflammatory disease. These roles are discussed in this review.


Focus on Inflammatory disease

Innate lymphoid cells in the initiation, regulation and resolution of inflammation pp698 - 708

Gregory F Sonnenberg & David Artis

doi:10.1038/nm.3892

The role of innate lymphoid cells (ILCs) in immune homeostasis and disease is reviewed.


Focus on Inflammatory disease

Influence of nutrient-derived metabolites on lymphocyte immunity pp709 - 718

Marc Veldhoen & Cristina Ferreira

doi:10.1038/nm.3894

Recent studies have provided insight into how the environment, and in particular the diet, influence the development of lymphocytes. Emerging studies indicate a role for this immune development in inflammatory disease.


Focus on Inflammatory disease

IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases pp719 - 729

Michele W L Teng, Edward P Bowman, Joshua J McElwee, Mark J Smyth, Jean-Laurent Casanova, Andrea M Cooper & Daniel J Cua

doi:10.1038/nm.3895

Cua and colleagues discuss the cellular and molecular rationale for targeting IL-12 and IL-23 for therapeutic purposes in inflammatory diseases; they also review existing clinical data, discuss potential side effects, and propose future directions for targeting these cytokines in additional disorders.


Focus on Inflammatory disease

Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies pp730 - 738

Judy H Cho & Marc Feldman

doi:10.1038/nm.3897

Recent advances in genetics have deepened our understanding of the pathogenic mechanisms behind autoimmune and immune-mediated diseases. This has revealed both shared pathways and a considerable degree of heterogeneity between diseases.


Top

Articles

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR pp741 - 750

Miguel Vizoso, Humberto J Ferreira, Paula Lopez-Serra, F Javier Carmona, Anna Martínez-Cardús, Maria Romina Girotti, Alberto Villanueva, Sonia Guil, Catia Moutinho, Julia Liz, Anna Portela, Holger Heyn, Sebastian Moran, August Vidal, Maria Martinez-Iniesta, Jose L Manzano, Maria Teresa Fernandez-Figueras, Elena Elez, Eva Muñoz-Couselo, Rafael Botella-Estrada, Alfonso Berrocal, Fredrik Pontén, Joost van den Oord, William M Gallagher, Dennie T Frederick, Keith T Flaherty, Ultan McDermott, Paul Lorigan, Richard Marais & Manel Esteller

doi:10.1038/nm.3863

Epigenetic inactivation of a Rab GTPase activating protein confers metastatic properties in melanoma, and it correlates with poor prognosis but better sensitivity to therapy by targeting EGFR signaling.


Subclonal diversification of primary breast cancer revealed by multiregion sequencing pp751 - 759

Lucy R Yates, Moritz Gerstung, Stian Knappskog, Christine Desmedt, Gunes Gundem, Peter Van Loo, Turid Aas, Ludmil B Alexandrov, Denis Larsimont, Helen Davies, Yilong Li, Young Seok Ju, Manasa Ramakrishna, Hans Kristian Haugland, Peer Kaare Lilleng, Serena Nik-Zainal, Stuart McLaren, Adam Butler, Sancha Martin, Dominic Glodzik, Andrew Menzies, Keiran Raine, Jonathan Hinton, David Jones, Laura J Mudie, Bing Jiang, Delphine Vincent, April Greene-Colozzi, Pierre-Yves Adnet, Aquila Fatima, Marion Maetens, Michail Ignatiadis, Michael R Stratton, Christos Sotiriou, Andrea L Richardson, Per Eystein Lønning, David C Wedge & Peter J Campbell

doi:10.1038/nm.3886

Whole-genome and targeted sequencing of multiple sections of each of 50 tumors reveals varying degrees of subclonal diversification and genomic heterogeneity.


Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes pp760 - 768

Ruidan Xue, Matthew D Lynes, Jonathan M Dreyfuss, Farnaz Shamsi, Tim J Schulz, Hongbin Zhang, Tian Lian Huang, Kristy L Townsend, Yiming Li, Hirokazu Takahashi, Lauren S Weiner, Andrew P White, Maureen S Lynes, Lee L Rubin, Laurie J Goodyear, Aaron M Cypess & Yu-Hua Tseng

doi:10.1038/nm.3881

Human brown and white preadipocyte clones from neck fat depots have been isolated and used to identify genetic biomarkers that predict their thermogenic capacity.

See also: News and Views by Boon et al.


Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion pp769 - 776

Talitha van der Meulen, Cynthia J Donaldson, Elena Cáceres, Anna E Hunter, Christopher Cowing-Zitron, Lynley D Pound, Michael W Adams, Andreas Zembrzycki, Kevin L Grove & Mark O Huising

doi:10.1038/nm.3872

Ucn3 is released from pancreatic beta cells along with insulin, and it engages a negative feedback loop by promoting somatostatin secretion from delta cells to control further insulin secretion.


Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension pp777 - 785

Lu Long, Mark L Ormiston, Xudong Yang, Mark Southwood, Stefan Gräf, Rajiv D Machado, Matthias Mueller, Bernd Kinzel, Lai Ming Yung, Janine M Wilkinson, Stephen D Moore, Kylie M Drake, Micheala A Aldred, Paul B Yu, Paul D Upton & Nicholas W Morrell

doi:10.1038/nm.3877

BMP9 activates signaling through the BMPR-II receptor in endothelial cells and reverses established disease in three animal models of pulmonary hypertension, thus pointing to a potential new treatment for this disease.


Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors pp786 - 794

Dario R Lemos, Farshad Babaeijandaghi, Marcela Low, Chih-Kai Chang, Sunny T Lee, Daniela Fiore, Regan-Heng Zhang, Anuradha Natarajan, Sergei A Nedospasov & Fabio M V Rossi

doi:10.1038/nm.3869

Tgf-β1 contributes to fibrosis during chronic injury by abrogating Tnf-directed apoptosis of fibro/adipogenic progenitor cells during muscle regeneration

See also: News and Views by Tidball & Wehling-Henricks


Top

Letters

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients pp795 - 801

Giulia Siravegna, Benedetta Mussolin, Michela Buscarino, Giorgio Corti, Andrea Cassingena, Giovanni Crisafulli, Agostino Ponzetti, Chiara Cremolini, Alessio Amatu, Calogero Lauricella, Simona Lamba, Sebastijan Hobor, Antonio Avallone, Emanuele Valtorta, Giuseppe Rospo, Enzo Medico, Valentina Motta, Carlotta Antoniotti, Fabiana Tatangelo, Beatriz Bellosillo, Silvio Veronese, Alfredo Budillon, Clara Montagut, Patrizia Racca, Silvia Marsoni, Alfredo Falcone, Ryan B Corcoran, Federica Di Nicolantonio, Fotios Loupakis, Salvatore Siena, Andrea Sartore-Bianchi & Alberto Bardelli

doi:10.1038/nm.3870

By monitoring ctDNA, the authors reveal the dynamic adaption of clonal populations in colorectal cancer patients treated with anti-EGFR therapy, suggesting that therapeutic re-challenge may have some benefit.

See also: News and Views by Meador & Lovly


Inhibition of amyloid-β plaque formation by α-synuclein pp802 - 807

Teresa Bachhuber, Natalie Katzmarski, Joanna F McCarter, Desiree Loreth, Sabina Tahirovic, Frits Kamp, Claudia Abou-Ajram, Brigitte Nuscher, Alberto Serrano-Pozo, Alexandra Müller, Marco Prinz, Harald Steiner, Bradley T Hyman, Christian Haass & Melanie Meyer-Luehmann

doi:10.1038/nm.3885

The introduction of α-synuclein into mouse models of Alzheimer's disease, either by intracerebral injection or transgenic overexpression, is found to inhibit the formation of hippocampal amyloid-β plaques.


Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization pp808 - 814

Di Fan, Laura A Coughlin, Megan M Neubauer, Jiwoong Kim, Min Soo Kim, Xiaowei Zhan, Tiffany R Simms-Waldrip, Yang Xie, Lora V Hooper & Andrew Y Koh

doi:10.1038/nm.3871

Andrew Koh and colleagues report that gut anaerobes in adult mice prevent Candida albicans colonization by inducing an antimicrobial peptide.


Diabetes primes neutrophils to undergo NETosis, which impairs wound healing pp815 - 819

Siu Ling Wong, Melanie Demers, Kimberly Martinod, Maureen Gallant, Yanming Wang, Allison B Goldfine, C Ronald Kahn & Denisa D Wagner

doi:10.1038/nm.3887

Neutraphil extracellular trap formation is increased in type 1 and 2 diabetes and impairs wound healing.


Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter pp820 - 826

Jing Wang, Chongxiu Sun, Norbert Gerdes, Conglin Liu, Mengyang Liao, Jian Liu, Michael A Shi, Aina He, Yi Zhou, Galina K Sukhova, Huimei Chen, Xian Wu Cheng, Masafumi Kuzuya, Toyoaki Murohara, Jie Zhang, Xiang Cheng, Mengmeng Jiang, Gary E Shull, Shaunessy Rogers, Chao-Ling Yang, Qiang Ke, Sabina Jelen, René Bindels, David H Ellison, Petr Jarolim, Peter Libby & Guo-Ping Shi

doi:10.1038/nm.3890

Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter.


Top

Errata

Erratum: Functionally defined therapeutic targets in diffuse intrinsic pontine glioma p827

Catherine S Grasso, Yujie Tang, Nathalene Truffaux, Noah E Berlow, Lining Liu, Marie-Anne Debily, Michael J Quist, Lara E Davis, Elaine C Huang, Pamelyn J Woo, Anitha Ponnuswami, Spenser Chen, Tessa B Johung, Wenchao Sun, Mari Kogiso, Yuchen Du, Lin Qi, Yulun Huang, Marianne Hütt-Cabezas, Katherine E Warren, Ludivine Le Dret, Paul S Meltzer, Hua Mao, Martha Quezado, Dannis G van Vuurden, Jinu Abraham, Maryam Fouladi, Matthew N Svalina, Nicholas Wang, Cynthia Hawkins, Javad Nazarian, Marta M Alonso, Eric H Raabe, Esther Hulleman, Paul T Spellman, Xiao-Nan Li, Charles Keller, Ranadip Pal, Jacques Grill & Michelle Monje

doi:10.1038/nm0715-827a


Erratum: Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients p827

Giulia Siravegna, Benedetta Mussolin, Michela Buscarino, Giorgio Corti, Andrea Cassingena, Giovanni Crisafulli, Agostino Ponzetti, Chiara Cremolini, Alessio Amatu, Calogero Lauricella, Simona Lamba, Sebastijan Hobor, Antonio Avallone, Emanuele Valtorta, Giuseppe Rospo, Enzo Medico, Valentina Motta, Carlotta Antoniotti, Fabiana Tatangelo, Beatriz Bellosillo, Silvio Veronese, Alfredo Budillon, Clara Montagut, Patrizia Racca, Silvia Marsoni, Alfredo Falcone, Ryan B Corcoran, Federica Di Nicolantonio, Fotios Loupakis, Salvatore Siena, Andrea Sartore-Bianchi & Alberto Bardelli

doi:10.1038/nm0715-827b


Top