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Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia
One of the five IL-17 receptors, IL-17RD lacks a motif thought to be required for downstream signalling. Melletet al. show that IL-17RD tunes IL-17A-dependent signalling; in its absence, MAPK signalling and neutrophil recruitment are impaired, but NF-κB activation is enhanced.
- Mark Mellett
- , Paola Atzei
- & Paul N. Moynagh
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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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The CD4+ T-cell help signal is transmitted from APC to CD8+ T-cells via CD27–CD70 interactions
CD8+ memory cytotoxic T lymphocytes need help from CD4+ T cells to undergo secondary expansion but the mechanisms of help are not fully understood. Here, it is shown that, after activation by CD4+ T cells, antigen-presenting cells activate CD8+T cells via the CD70/CD27 co-stimulatory pathway.
- Sonia Feau
- , Zacarias Garcia
- & Stephen P. Schoenberger
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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 AccessBCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway
Class switch recombination diversifies antibody effector functions and requires expression of activation-induced cytidine deaminase (AID). In this study, ligation of the B-cell receptor and Toll-like receptors synergize to induce non-canonical NF-κB activation, AID expression and class switching recombination.
- Egest J. Pone
- , Jinsong Zhang
- & Paolo Casali
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The GOLD domain-containing protein TMED7 inhibits TLR4 signalling from the endosome upon LPS stimulation
TLRs have a role in innate immunity and TLR4 recognizes lipopolysaccharide on the cell wall of Gram-negative bacteria. Now, Doyle and colleagues show that a transmembrane protein TMED7, similar to aDrosophilahomologue, can negatively control TLR4 signalling, suggesting a conserved role in innate immunity.
- Sarah L. Doyle
- , Harald Husebye
- & Anne F. McGettrick
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| Open AccessProstaglandin E2 and SOCS1 have a role in intestinal immune tolerance
The gut is populated by a myriad of microorganisms and how the immune system tolerates their presence is of great interest. Here, by studying colon morphology in multiple knockout mice, the authors demonstrate a potential role for prostaglandin E2 and SOCS1 in mediating immune tolerance.
- Takatoshi Chinen
- , Kyoko Komai
- & Akihiko Yoshimura