Inflammatory diseases

  • Article
    | Open Access

    T regulatory (Treg) cells can differentiate into effector Treg (eTreg) cells that might be functional in inflammatory diseases. Using RNA sequencing and epigenetic profiling, the authors show that eTreg signatures in juvenile idiopathic arthritis joints are similar to tumour microenvironment (TME) Treg cells and are affected by tissue-specific epigenetic regulation.

    • Gerdien Mijnheer
    • , Lisanne Lutter
    •  & Femke van Wijk
  • Article
    | Open Access

    Asthma is caused by hyperreactivity to benign antigens, with humoral immunity orchestrated by interleukin-4 (IL-4) and IL-13 being the key etiological factor. Here the authors show, in humanized mouse models, that dual vaccination against IL-4 and IL-13 induces their durable suppression ameliorate experimental asthma, and to hint clinical translation.

    • Eva Conde
    • , Romain Bertrand
    •  & Laurent L. Reber
  • Article
    | Open Access

    Glycoprotein-2 (GP-2) can protect the intestinal epithelial barrier from bacteria and is associated with protection against Crohn’s disease. Here, the authors show pancreatic GP-2 is the source of the intestine’s luminal GP-2 that binds bacteria and prevents them from attaching to the epithelium, also limiting pathology in a DSS colitis mouse model.

    • Yosuke Kurashima
    • , Takaaki Kigoshi
    •  & Hiroshi Kiyono
  • Article
    | Open Access

    RIPK1 is a critical kinase which mediates necroptosis, apoptosis and inflammation. Regulation of RIPK1 by ubiquitination is being intensively investigated. Here, the authors made knock-in RIPK1-K612R mice and demonstrate that this mutation alters the RIPK1 ubiquitinylation pattern and inhibits its prodeath kinase activity in response to TNFα but sensitizes cell death to TLRs signals.

    • Xingyan Li
    • , Mengmeng Zhang
    •  & Junying Yuan
  • Article
    | Open Access

    Chronic obstructive pulmonary disease (COPD) is a progressing disease, with lung but not gut microbiota implicated in its etiology. Here the authors compare the stool from patients with COPD and healthy controls to find specific gut bacteria and metabolites associated with active disease, thereby hinting at a potential role for the gut microbiome in COPD.

    • Kate L. Bowerman
    • , Saima Firdous Rehman
    •  & Philip M. Hansbro
  • Article
    | Open Access

    Asthma is a common disease of the airways for which numerous genetic loci have been identified. Here, Han et al. carry out a genome-wide analysis for asthma to identify additional loci, report sex-stratified and genetic risk score analyses, and functionally follow-up one locus using a murine model of airway hyperreactivity.

    • Yi Han
    • , Qiong Jia
    •  & Hooman Allayee
  • Article
    | Open Access

    Food allergy is triggered by IgE, but some individuals are not allergic to peanuts despite making peanut-specific IgE, and are considered peanut-tolerant. Here, the authors identify differences in blood immune cell composition of peanut-allergic and tolerant infants using mass cytometry, which may help uncover the mechanism of allergic tolerance.

    • Melanie R. Neeland
    • , Sandra Andorf
    •  & Kari C. Nadeau
  • Article
    | Open Access

    Innate lymphoid cells (ILC) are important immune cells for maintaining the gut homeostasis. Here the authors show that c-FLIP, an anti-apoptotic molecule, is important for the development of NKP46+ ILC1, including conventional natural killer (cNK) cells, and ILC3, with cNK being more critical for ameliorating intestinal inflammation.

    • Ute Bank
    • , Katrin Deiser
    •  & Thomas Schüler
  • Article
    | Open Access

    Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

    • Eva Gonçalves Serra
    • , Tobias Schwerd
    •  & Carl A. Anderson
  • Article
    | Open Access

    Here, the authors present the results of a mother–child cohort randomized clinical trial of n-3 LCPUFA and vitamin D maternal supplementation, finding an association between supplement-induced microbiota changes in infant airways at age 1-month but not the infant fecal or maternal vaginal microbiome.

    • Mathis H. Hjelmsø
    • , Shiraz A. Shah
    •  & Hans Bisgaard
  • Article
    | Open Access

    Systemic autoinflammatory syndromes such as cryopyrin-associated periodic syndrome (CAPS) are rare and often involve genes related to the inflammasome. Here, the authors report a syndrome characterised by systemic inflammation and cold-induced urticarial rash associated with a Factor XII-activating mutation.

    • Jörg Scheffel
    • , Niklas A. Mahnke
    •  & Karoline Krause
  • Article
    | Open Access

    Immunoglobulin E (IgE) plays a central role in allergic responses, yet therapeutic targeting of IgE with antibodies such as omalizumab is met with various limitations. Here the authors characterize the molecular properties and crystal structure of a new anti-IgE antibody, ligelizumab, for mechanistic insights related to its enhanced suppression activity.

    • Pascal Gasser
    • , Svetlana S. Tarchevskaya
    •  & Alexander Eggel
  • Article
    | Open Access

    ‘Missing self’ is a mode of natural killer (NK) cell activation aimed to detect the lack of HLA-I molecules on infected or neoplastic cells. Here, the authors show that mismatch between donor HLA-I and cognate receptors on recipient NK cells mediates microvascular inflammation-associated graft rejection, a pathology that is preventable by mTOR inhibition.

    • Alice Koenig
    • , Chien-Chia Chen
    •  & Olivier Thaunat
  • Article
    | Open Access

    Allergic asthma symptoms may be controlled, but currently no effective therapy exist to address the underlying pathology. Here the authors show, using mouse model of adoptive cell transfer, that CD4-CD8- T cells can suppress the function of dendritic cells and T follicular helper cells via Lag3 to provide allergen-specific protection from asthma.

    • Dan Tian
    • , Lu Yang
    •  & Dong Zhang
  • Article
    | Open Access

    Neutrophils and macrophages are both involved in the initiation of inflammation, but whether and how they may participate in inflammation resolution is unclear. Here the authors show that neutrophils may mediate the conversion of macrophage into a pro-resolution phenotype via reactive oxygen species production to promote liver repair.

    • Wenting Yang
    • , Yuandong Tao
    •  & Li Tang
  • Article
    | Open Access

    The JAK-STAT signaling pathway is important for cytokine responses and CD4 T-cell differentiation. Here the authors show that Stat1 also serves to protect CD4 T cells from natural killer cell-mediated killing, potentially by promoting the expression of Nlrc5 and MHC-I, to preserve the induction of experimental colitis via the adoptive transfer of CD4 T cells.

    • Yu Hui Kang
    • , Amlan Biswas
    •  & Scott B. Snapper
  • Article
    | Open Access

    Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here the authors use ~40 nm cationic nanoparticles to scavenge cfDNA, and demonstrate the potential for nanomedicine to relieve debilitating RA symptoms.

    • Huiyi Liang
    • , Bo Peng
    •  & Yongming Chen
  • Article
    | Open Access

    Activation of the NLRP3 inflammasome triggers the production of inflammatory cytokines. Here, the authors inactivate NLRP3 in macrophages using CRISPR/Cas9 encapsulated in nanoparticles, and show that administration in mice is effective in preventing septic shock and peritonitis, and in improving diabetes-associated inflammation and insulin resistance.

    • Congfei Xu
    • , Zidong Lu
    •  & Jun Wang
  • Article
    | Open Access

    Eosinophils are important mediators of allergic responses, but how they are recruited to the inflamed site is still unclear. Here the authors show that CD103+ cDC1 cells secrete CCL17 and CCL22 for eosinophil recruitment, with this process promoted by CD24CD11b+ DC2s in the early phase but suppressed by CD24+ cDC2s in the late phase.

    • Shuying Yi
    • , Jing Zhai
    •  & Hua Tang
  • Article
    | Open Access

    Vitamin E metabolites are proposed to have signalling capacity, but how they may regulate immune responses is still unclear. Here the authors show that a vitamin E metabolite, α-T-13′-COOH, can inhibit 5-lipoxygenase and thereby suppress the synthesis of lipid mediators of immune activation and inflammatory responses.

    • Helmut Pein
    • , Alexia Ville
    •  & Andreas Koeberle
  • Article
    | Open Access

    Understanding how regulators of inflammation affect nucleic acid sensing is important for targeting research against inflammatory diseases and conditions. Here, the authors identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells.

    • David Olagnier
    • , Aske M. Brandtoft
    •  & Christian K. Holm
  • Article
    | Open Access

    Pulmonary alveolar proteinosis (PAP) is associated with defective macrophage clearance of surfactant. Here, the authors show that patients with PAP have altered cholesterol-to-phospholipid ratio in their surfactant, and that more importantly, statin therapy and reduction of cholesterol accumulation in macrophages can ameliorate PAP in both humans and mice.

    • Cormac McCarthy
    • , Elinor Lee
    •  & Bruce C. Trapnell
  • Article
    | Open Access

    Lymphotoxin beta receptor (LTβR) signalling regulates leukocyte migration through the lymphatic endothelial layers. Here, the authors show that treatment of an LTβR-derived decoy peptide can target the non-classical NFκB pathway to inhibit T cell and dendritic cell migration and ameliorate contact hypersensitivity in mouse models.

    • Wenji Piao
    • , Yanbao Xiong
    •  & Jonathan S. Bromberg
  • Article
    | Open Access

    Allergen-specific immunotherapy is used to treat patients affected by acute immunoglobulin E (IgE) responses, but the function mechanism is unclear. Here the authors show that the administration of two cat allergen-specific IgGs reduces allergic responses in mouse models and helps ameliorate clinical symptoms in a phase 1b clinical trial.

    • J. M. Orengo
    • , A. R. Radin
    •  & G. D. Yancopoulos
  • Article
    | Open Access

    Matrix metalloproteinases (MMP) are involved in vascular remodeling associated with plaque progression. Little is known about their immune regulatory role in vascular disorders. Here, the authors report that MT4-MMP-deficiency increases the recruitment of patrolling monocytes to early atherosclerotic lesions, which accelerates atherosclerosis.

    • Cristina Clemente
    • , Cristina Rius
    •  & Alicia G. Arroyo
  • Article
    | Open Access

    Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.

    • Ailing Liu
    • , Minhui Chen
    •  & Lisa Borghesi
  • Article
    | Open Access

    Colonization of commensal bacteria is thought to impact immune development, especially in the earliest years of life. Here, the authors show, by analyzing the development of the gut microbiome of 690 children, that microbial composition at the age of 1 year is associated with asthma diagnosed in the first 5 years of life.

    • Jakob Stokholm
    • , Martin J. Blaser
    •  & Hans Bisgaard
  • Article
    | Open Access

    The pathogenesis of paradoxical psoriasis in patients receiving anti-TNF treatments for classical psoriasis is unclear. Here, the authors show that anti-TNF drugs enhance the production of type I interferon by plasmacytoid dendritic cells, causing skin lesions that, unlike classical psoriasis, lack T- cell autoimmunity.

    • Curdin Conrad
    • , Jeremy Di Domizio
    •  & Michel Gilliet
  • Article
    | Open Access

    IgE is linked to allergic diseases and there is a great interest in developing anti-IgE therapeutics. Here the authors characterize the binding of human IgE Fc to a single domain antibody (sdab) and show that the sdab induces a closed conformation, which prevents and disrupts IgE binding to its receptor FcεRI and abrogates allergen mediated activation.

    • Frederic Jabs
    • , Melanie Plum
    •  & Edzard Spillner
  • Article
    | Open Access

    Nucleic acid sensing is important to ensure that an innate immune response is only mounted against microbial nucleic acid. Here, the authors identify loss-of-function mutations in the DNASE2 gene that cause type I interferon-mediated autoinflammation due to enhanced systemic interferon signaling.

    • Mathieu P. Rodero
    • , Alessandra Tesser
    •  & Yanick J. Crow
  • Article
    | Open Access

    The NLRP3 inflammasome is central to a variety of inflammatory diseases, but how it is regulated to prevent excessive inflammation is not clear. Here the authors show that NLRP3 activation causes SHP2 translocation to the mitochondria to interact with and dephosphorylate ANT1, thus stabilizing the mitochondria and preventing release of proinflammatory mitochondrial DNA and ROS.

    • Wenjie Guo
    • , Wen Liu
    •  & Qiang Xu
  • Article
    | Open Access

    Rising rates of peanut allergy pose a public health problem. Here, the authors profile blood transcriptomes during double-blind, placebo-controlled oral challenge in peanut-allergic children to identify gene and cell composition changes, and construct causal networks to detect key allergic reaction drivers.

    • C. T. Watson
    • , A. T. Cohain
    •  & S. Bunyavanich
  • Article
    | Open Access

    IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.

    • Jin-Shu He
    • , Sharrada Subramaniam
    •  & Maria A. Curotto de Lafaille
  • Article
    | Open Access

    Non-invasive cell tracking is a powerful method to visualize cells in vivo under physiological and pathophysiological conditions. Here Thunemann et al. generate a mouse model for in vivo tracking and quantification of specific cell types by combining a PET reporter gene with Cre-dependent activation that can be exploited for any cell population for which a Cre mouse line is available.

    • Martin Thunemann
    • , Barbara F. Schörg
    •  & Robert Feil
  • Article
    | Open Access

    TWEAK is a TNF family member that binds the NFκB signalling receptor Fn14. Here the authors show that TWEAK is central to skin inflammation in mouse models of atopic dermatitis and psoriasis and causes similar pathology when injected subcutaneously into mice.

    • Daniel Sidler
    • , Ping Wu
    •  & Michael Croft
  • Article
    | Open Access

    ARPC1B is a component of the actin-related protein 2/3 complex (Arp2/3), which is required for actin filament branching. Kahret al. show that ARPC1B deficiency in humans is associated with severe multisystem disease that includes platelet abnormalities, eosinophilia, eczema and other indicators of immune disease.

    • Walter H. A. Kahr
    • , Fred G. Pluthero
    •  & Aleixo M Muise
  • Article
    | Open Access

    IL-12 and IL-23 share the common p40 subunit yet have distinct immunological functions with IL-12 typically contributing to Th1 responses and IL-23 to Th17 responses. Here the authors show that current p40 based therapies for psoriasis are counterproductive owing to an IFN-γ-independent tissue protective function of IL-12 in skin.

    • Paulina Kulig
    • , Stephanie Musiol
    •  & Burkhard Becher
  • Article
    | Open Access

    Angiopoietin-like 4 protein (ANGPTL4) is a regulator of lipoprotein metabolism whose role in atherosclerosis has been controversial. Here the authors show that ANGPTL4 deficiency in haematopoietic cells increases atherogenesis by promoting myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

    • Binod Aryal
    • , Noemi Rotllan
    •  & Carlos Fernández-Hernando
  • Article
    | Open Access

    Endothelial to mesenchymal transition (EndMT) is a crucial developmental process that also plays a role in the pathogenesis of some diseases. Here the authors show that EndMT contributes to the development of atherosclerosis in mice and humans, and is associated with complex human plaques that may be prone to rupture.

    • Solene M. Evrard
    • , Laura Lecce
    •  & Jason C. Kovacic