Immunological disorders

  • Article
    | Open Access

    Protein scaffolds can serve as alternatives to antibodies in a range of applications. Here, the authors report the design and development of Alphabody™, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold that the authors use to develop Alphabodies that can neutralize human IL-23 with high specificity and affinity.

    • Johan Desmet
    • , Kenneth Verstraete
    •  & Savvas N. Savvides
  • Article
    | Open Access

    The mechanism by which NAD+ alters the systemic immune response is unclear. Here the authors show that NAD+ induces systemic homeostasis and protects against experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, by regulating CD4+T cell differentiation and promoting myelin and axonal regeneration.

    • Stefan G. Tullius
    • , Hector Rodriguez Cetina Biefer
    •  & Abdallah ElKhal
  • Article |

    Genetic studies have connected polymorphisms in the IL-2 receptor alpha (IL2RA) gene with susceptibility to multiple sclerosis, but the mechanisms underlying this association are not clear. Here, the authors show that a polymorphism in IL2RA increases responsiveness to IL-2 and GM-CSF production in human THcells.

    • Felix J. Hartmann
    • , Mohsen Khademi
    •  & Burkhard Becher
  • Article |

    Aetiology of colitis is highly complex and incompletely understood. Here the authors show in mouse models that A20 deubiquitinase limits pro-inflammatory cytokine production in myeloid cells while inhibiting proapoptotic response to these cytokines in enterocytes, and that only upon losing both functions intestinal pathologies develop.

    • Lars Vereecke
    • , Sara Vieira-Silva
    •  & Geert van Loo
  • Article |

    Macrophages can be polarized to inflammatory M1 and anti-inflammatory M2 phenotypes, depending on the cytokine milieu. Here, Zhu et al.demonstrate that tuberous sclerosis complex 1 (TSC1) inhibits M1 and promotes M2 polarization of macrophages to prevent inflammatory disorders.

    • Linnan Zhu
    • , Tao Yang
    •  & Yong Zhao
  • Article |

    The mechanisms controlling Th2-mediated inflammation are not well defined. Here the authors show that the E3 ubiquitin ligase Grail is involved in a negative feedback loop with Th2-specific transcription factors and regulates Th2-mediated allergic asthma responses.

    • Anupama Sahoo
    • , Andrei Alekseev
    •  & Roza Nurieva
  • Article |

    Mcl-1 is an important survival factor for several hematopoietic lineages including B and T lymphocytes, but its role in the Natural Killer (NK) cells has not been previously tested. Here, the authors report that deletion of Mcl-1 in the NK cell lineage leads to the loss of NK cells from all tissues.

    • Priyanka Sathe
    • , Rebecca B. Delconte
    •  & Nicholas D. Huntington
  • Article |

    Th9 cells are a subset of T helper cells that protect hosts against helminthic infection, but can also mediate allergic disease through overexpression of the cytokine IL-9. Here, Niedbala et al.show that nitric oxide is a potent enhancer of Th9 differentiation via the activation of p53 protein.

    • Wanda Niedbala
    • , Anne-Gaelle Besnard
    •  & Foo Y. Liew
  • Article
    | Open Access

    Alarmins are locally released during inflammation and are early amplifiers of inflammation. Here Vogl et al.show that the alarmin S100A8/S100A9 can be used as a sensitive marker to detect subclinical inflammation and follow disease progression in a variety of disease models.

    • Thomas Vogl
    • , Michel Eisenblätter
    •  & Johannes Roth
  • Article
    | Open Access

    The advancement of sensitive, accurate and non-invasive methods to identify the allergen that drives allergic disease in an individual remains a challenge. Here, the authors develop a synthetic biology approach using human designer cells to profile allergic reactions against an array of allergens measuring histamine release from whole blood.

    • David Ausländer
    • , Benjamin Eggerschwiler
    •  & Martin Fussenegger
  • Article |

    Although psoriasis is a chronic disorder affecting approximately 2% of the population, little is known about the underlying genetic architecture. Here, the authors carry out exome sequencing in a large Han Chinese cohort of psoriasis patients and healthy controls, and identify three new genes that may increase risk of developing the disease.

    • Yujun Sheng
    • , Xin Jin
    •  & Xuejun Zhang
  • Article |

    Acne vulgarisis a common, inflammatory skin disorder. Here the authors carry out a genome-wide association study and identify three genetic variants that associate with an increased risk of developing acne, which together suggest a mechanistic role for the TGFβ cell signalling pathway in acne development and progression.

    • Alexander A. Navarini
    • , Michael A. Simpson
    •  & Jonathan N. Barker
  • Article
    | Open Access

    Coeliac disease is characterized by an inappropriate immune response to dietary gluten proteins, involving the production of antibodies reactive to gluten. Here, the authors study the intestinal antibody response against gluten and show that gluten-specific antibodies have a low degree of somatic hypermutations.

    • Øyvind Steinsbø
    • , Carole J. Henry Dunand
    •  & Ludvig M. Sollid
  • Article |

    Nucleic acids modulate T cell responses; however, the physiological significance of this property remains unclear. Here, the authors show that self-DNA complexes with antimicrobial peptides or histones, which mediates T cell costimulation to induce Th2 cell differentiation.

    • Takayuki Imanishi
    • , Chitose Ishihara
    •  & Takashi Saito
  • Article |

    Single nucleotide polymorphisms in the gene encoding the protein phosphatase PTPN2 are associated with autoimmunity in humans. Here, Wiede et al. show that PTPN2 suppresses the proliferative capacity of T cells in lymphopenia and prevents the development of autoimmunity resulting from overt homoeostatic proliferation.

    • Florian Wiede
    • , Nicole L. La Gruta
    •  & Tony Tiganis
  • Article |

    In the early stages of atherosclerosis, macrophages in the vessel wall convert into foam cells, which promote the rise of atherosclerotic plaques. Here Hamada et al. show that the macrophage transcription factor MafB inhibits foam-cell apoptosis, and that its absence promotes atherosclerosis development in mice.

    • Michito Hamada
    • , Megumi Nakamura
    •  & Satoru Takahashi
  • Article |

    Severe acne is a common skin disease characterized by chronic inflammation and potential scarring. Here, the authors have identified genetic variants at two loci associated with severe acne and provide insight into the genetic architecture and biological pathways underlying the disease.

    • Li He
    • , Wen-Juan Wu
    •  & Ya-Ping Zhang
  • Article |

    Autoimmune T cell receptors can interact with both self and microbial antigens, but the structural basis for crossreactivity is not fully understood. Here, the authors provide structural insights into binding characteristics of the autoreactive T cell receptor Hy.1B11 to both self and pathogen-derived peptides.

    • Dhruv K. Sethi
    • , Susana Gordo
    •  & Kai W. Wucherpfennig
  • Article |

    ORMDL3has been identified as a gene associated with asthma susceptibility, but its exact role in the pathogenesis of this disease is not well known. Here, the authors propose that induction of ORMDL3 in eosinophils modulates the expression of integrins, which could contribute to a key inflammatory event in asthma.

    • Sung Gil Ha
    • , Xiao Na Ge
    •  & P. Sriramarao
  • Article |

    Intestinal infection with adherent-invasive Escherichia coliis associated with Crohn’s disease in humans; however, its functional role remains unclear, in part due to a lack of animal models, which sustain chronic disease. Here the authors establish such a model in mice and show that it shares features with human Crohn’s disease.

    • Cherrie-Lee N. Small
    • , Sarah A. Reid-Yu
    •  & Brian K. Coombes
  • Article
    | Open Access

    Mouse models of arthritis generally do not result in both chronic disease and autoantibody production—two key features of the human disease. Here the authors obtain both features by combining two common protocols, and find that disease severity is associated with the presence of a previously unidentified lymph node.

    • Uta Baddack
    • , Sven Hartmann
    •  & Gerd Müller
  • Article |

    Inositol polyphosphate 4 phosphatase regulates phosphoinositide signalling and is associated with an increased risk of asthma. Aichet al. show that, in a mouse model of airway inflammation, calpains degrade inositol polyphosphate 4 phosphatase resulting in exacerbated phosphoinositide 3-kinase signalling.

    • Jyotirmoi Aich
    • , Ulaganathan Mabalirajan
    •  & Balaram Ghosh
  • Article
    | Open Access

    Complex diseases such as multiple sclerosis have both genetic and environmental components. This study demonstrates that variants of genes implicated in multiple sclerosis, and alterations in cellular metabolism and vitamin D3 levels, alterN-glycosylation, a post-translational modification causal of the disease in mice.

    • Haik Mkhikian
    • , Ani Grigorian
    •  & Michael Demetriou
  • Article
    | Open Access

    HIV infection can be partially regulated by the host immune system; however whether B cells contribute to this response is unclear. Huanget al. show that transient depletion of B cells can result in an increase in HIV viral load suggesting that these immune cells do participate in the control of HIV infection.

    • Kuan-Hsiang G. Huang
    • , David Bonsall
    •  & Paul Klenerman