IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease

Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC), IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease.     

Learning and discrimination of individual cuticular hydrocarbons by honeybees (Apis mellifera)

In social insect colonies, recognition of nestmates, kinship, caste and reproductive status is crucial both for individuals and for the colony. The recognition cues used are thought to be chemical, with the hydrocarbons found on the cuticle of insects often cited as being particularly important. However, in honeybees (Apis mellifera) the role of cuticular hydrocarbons in nestmate recognition is controversial. Here we use the proboscis extension response (PER) conditioning paradigm to determine how well honeybees learn long-chain linear alkanes and (Z)-alkenes present on the cuticle of worker bees, and also how well they can discriminate between them. We found large differences both in learning and discrimination abilities with the different cuticular hydrocarbons. Thus, the tested hydrocarbons could be classified into those which the bees learnt and discriminated well (mostly alkenes) and those which they did not (alkanes and some alkenes). These well-learnt alkenes may constitute important compounds used as cues in the social recognition processes.     

Systemic response to aphid infestation by <Emphasis Type="Italic">Myzus persicae</Emphasis> in the phloem of <Emphasis Type="Italic">Apium graveolens</Emphasis>

Little is known about the molecular processes involved in the phloem response to aphid feeding. We investigated molecular responses to aphid feeding on celery (Apium graveolenscv. Dulce) plants infested with the aphid Myzus persicae, as a means of identifying changes in phloem function. We used celery as our model species as it is easy to separate the phloem from the surrounding tissues in the petioles of mature leaves of this species. We generated a total of 1187 expressed sequence tags (ESTs), corresponding to 891 non-redundant genes. We analysed these ESTs in silico after cDNA macroarray hybridisation. Aphid feeding led to significant increase in RNA accumulation for 126 different genes. Different patterns of deregulation were observed, including transitory or stable induction 3 or 7days after infestation. The genes affected belonged to various functional categories and were induced systemically in the phloem after infestation. In particular, genes involved in cell wall modification, water transport, vitamin biosynthesis, photosynthesis, carbon assimilation and nitrogen and carbon mobilisation were up-regulated in the phloem. Further analysis of the response in the phloem or xylem suggested that a component of the response was developed more specifically in the phloem. However, this component was different from the stress responses in the phloem driven by pathogen infection. Our results indicate that the phloem is actively involved in multiple adjustments, recruiting metabolic pathways and in structural changes far from aphid feeding sites. However, they also suggest that the phloem displays specific mechanisms that may not be induced in other tissues.EST, macroarray and clustering data are available from our website [http://www-biocel.versailles.inra.fr/phloem]. Data deposition: The sequences reported in this paper have been deposited in the Genbank database (Accession nos.: AY607692-AY607700, AY611007, CN253939-CN255151, CV512445-CV512447 and CV651120-CV651121).     

Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?

Background

Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats.

Methods

Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45^- CD73⁺ CD90⁺ MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure.

Results

A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed in vivo bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group.

Conclusion

Adhesive BM-derived CD45^- CD73⁺ CD90⁺ MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions.     

Perceptual and neural olfactory similarity in honeybees

The question of whether or not neural activity patterns recorded in the olfactory centres of the brain correspond to olfactory perceptual measures remains unanswered. To address this question, we studied olfaction in honeybees Apis mellifera using the olfactory conditioning of the proboscis extension response. We conditioned bees to odours and tested generalisation responses to different odours. Sixteen odours were used, which varied both in their functional group (primary and secondary alcohols, aldehydes and ketones) and in their carbon-chain length (from six to nine carbons).The results obtained by presentation of a total of 16 × 16 odour pairs show that (i) all odorants presented could be learned, although acquisition was lower for short-chain ketones; (ii) generalisation varied depending both on the functional group and the carbon-chain length of odours trained; higher generalisation was found between long-chain than between short-chain molecules and between groups such as primary and secondary alcohols; (iii) for some odour pairs, cross-generalisation between odorants was asymmetric; (iv) a putative olfactory space could be defined for the honeybee with functional group and carbon-chain length as inner dimensions; (v) perceptual distances in such a space correlate well with physiological distances determined from optophysiological recordings of antennal lobe activity. We conclude that functional group and carbon-chain length are inner dimensions of the honeybee olfactory space and that neural activity in the antennal lobe reflects the perceptual quality of odours.     

Depolarization activates ERK and proline-rich tyrosine kinase 2 (PYK2) independently in different cellular compartments in hippocampal slices

In the hippocampus, extracellular signal-regulated kinase (ERK) and the non-receptor protein proline-rich tyrosine kinase 2 (PYK2) are activated by depolarization and involved in synaptic plasticity. Both are also activated under pathological conditions following ischemia, convulsions, or electroconvulsive shock. Although in non-neuronal cells PYK2 activates ERK through the recruitment of Src-family kinases (SFKs), the link between these pathways in the hippocampus is not known. We addressed this question using K(+)-depolarized rat hippocampal slices. Depolarization increased the phosphorylation of PYK2, SFKs, and ERK. These effects resulted from Ca(2+) influx through voltage-gated Ca(2+) channels and were diminished by GF109203X, a protein kinase C inhibitor. Inhibition of SFKs with PP2 decreased PYK2 tyrosine phosphorylation dramatically, but not its autophosphorylation on Tyr-402. Moreover, PYK2 autophosphorylation and total tyrosine phosphorylation were profoundly altered in fyn-/- mice, revealing an important functional relationship between Fyn and PYK2 in the hippocampus. In contrast, ERK activation was unaltered by PP2, Fyn knock-out, or LY294002, a phosphatidyl-inositol-3-kinase inhibitor. ERK activation was prevented by MEK inhibitors that had no effect on PYK2. Immunofluorescence of hippocampal slices showed that PYK2 and ERK were activated in distinct cellular compartments in somatodendritic regions and nerve terminals, respectively, with virtually no overlap. Activation of ERK was critical for the rephosphorylation of a synaptic vesicle protein, synapsin I, following depolarization, underlining its functional importance in nerve terminals. Thus, in hippocampal slices, in contrast to cell lines, depolarization-induced activation of non-receptor tyrosine kinases and ERK occurs independently in distinct cellular compartments in which they appear to have different functional roles.