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MafB promotes atherosclerosis by inhibiting foam-cell apoptosis
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
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A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation
Inflammatory processes in atherosclerotic lesions promote disease progression and plaque rupture. Here the authors load the drug statin into nanoparticles made of recombinant high-density lipoprotein and show that these accumulate in atherosclerotic plaques and reduce plaque inflammation in mice.
- Raphaël Duivenvoorden
- , Jun Tang
- & Willem J. M. Mulder
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Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne
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
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Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation
Allergic airway inflammation in asthma can be treated with corticosteroids, but some patients remain unresponsive to this therapy. Here, Kabata et al. show that thymic stromal lymphopoietin contributes to the corticosteroid resistance during airway inflammation through its action on natural helper cells.
- Hiroki Kabata
- , Kazuyo Moro
- & Koichiro Asano
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Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop
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
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ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
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
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| Open AccessGenome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering
The pathogenesis of inflammatory disorders afflicting the skin is multifactorial. Srinivas et al. show that diversity of the skin microbiota is a critical factor determining the susceptibility to epidermolysis bullosa acquisita, a chronic mucocutaneous autoimmune skin blistering disease.
- Girish Srinivas
- , Steffen Möller
- & Saleh M. Ibrahim
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Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis
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
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| Open AccessA chronic model of arthritis supported by a strain-specific periarticular lymph node in BALB/c mice
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
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| Open AccessGRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance
The clearance of apoptotic cells by macrophages is important for tissue homoeostasis. Here Nakaya et al. reveal a role for GRK6 in the regulation of apoptotic engulfment and show that GRK6 deficiency in mice leads to autoimmune disease and iron accumulation in the spleen.
- Michio Nakaya
- , Mitsuru Tajima
- & Hitoshi Kurose
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| Open AccessEpidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice
Phospholipase C is a signalling molecule with many cellular functions, but its physiological role at the organismal level is largely unknown. Kanemaruet al.show that phospholipase Cδ1 in the mouse epidermis influences interleukin and leukocyte concentrations in the blood.
- Kaori Kanemaru
- , Yoshikazu Nakamura
- & Kiyoko Fukami
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Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation
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
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| Open AccessGenetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis
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
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| Open AccessB-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection
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