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LAB WATCH Jean-Philippe.Girard@ipbs.fr corinne.cayrol@ipbs.fr 11 WINTER 2015 N° 36 Biology Muffling a Whistleblower BY CLEMENTINE WALLACE Asthma, rhinitis, food reactions… The prevalence of allergic diseases has increased dramatically in the past two decades, especially among children. Yet existing medication is not effective in all patients and experts are seeking new therapeutic options. About a decade ago, researchers from the IPBS1 discovered a molecule, known as interleukin-33 (IL-33), essential in activating the cascade of immune responses observed in allergic reactions. Now, in a new study,2 the team describes the mechanisms by which IL-33 transmits its alarm signal. When the organism detects what it considers a harmful intruder—such as dust mites, pollen, or mold—tissues like the lung release IL-33 into the bloodstream. Working in vitro, the researchers demonstrated that certain white blood cells, called mast cells, then release enzymes, which cleave IL-33 into what the authors call its “hyperactive” form. “We use the word ‘hyperactive’ because, in our lab experiments, it proved 30 times more potent than the initial form in activating cells of the type-2 immune system, whose role is to get rid of the allergen,” says senior author Jean-Philippe Girard. “This activation is what triggers allergic symptoms like inflammation of the airways.” When using generic enzyme inhibitors in vitro, the team observed that mast cells could no longer trim away IL-33. When these inhibitors were injected inside living mice, the animals’ immune reactions to a common fungal allergen were significantly reduced. “Targeting mast cell enzymes could be a new mechanism to prevent the outbreak of allergic reactions,” concludes study co-author Corinne Cayrol.1 ii Undersea earthquakes, which can cause devastating tsunamis, are set off by tectonic plate movement. But what mechanisms at work locally precede and trigger their shocks? To answer this question, a French-US team, including researchers from the CNRS, IFREMER,1 and IFSTTAR,2 used Northeast Pacific subsea data to build a theoretical model of fluids flowing in the seabed at a transform fault3 as the latter evolves from stability to seism.4 Not only do results explain the process leading to subsea quakes, they also point to a principle likely to apply to other terrains. According to the study, the timing of quakes relies on the properties of seabed fluids: specifically, shocks Image showing the IL-33 protein (red) produced at high levels in blood vessels (green). are triggered by a change in the compressibility of these fluids. Seisms are in fact deferred as long as the tectonic stress that weakens the bedrock is offset by a suction-cup effect in the pores between the beds—an effect that study co-author Pierre Henry of the CEREGE5 likens to the way “wet sand on a beach seems harder than dry sand because seawater fills the spaces between sand grains.” This effect is strongest when fluids are hard-tocompress liquids, lowest when they are compressible gases. Yet seabed fluids may also be supercritical, halfway between gas and liquid, due to the high pressure and heat of the magma rising from nearby © J.-P. GIRARD, IPBS/CNRS/UNIVERSITÉ TOULOUSE III - PAUL SABATIER mid-ocean ridges. In this state, their compressibility varies with pressure, and if such a shift occurs during a fault slip, the suction-cup effect will fail, causing a mainshock. Venturing beyond the subsea quakes in the study, Henry suggests that “change in fluid compressibility is the phenomenon’s key factor, independently of its marine context.” His next challenge is thus to “hunt down and demonstrate the mechanism in non-marine environments,” for example Iceland’s supercritical geothermal zones. ii Earth Sciences Tremors of the Deep BY FUI LEE LUK 1. Institut français de recherche pour l’exploitation de la mer. 2. Institut français des sciences et technologies des transports, de l’aménagement et des réseaux. 3. Type of fault between two tectonic plates that slide horizontally past one another. 4. L. Géli et al., “Seismic precursors linked to super-critical fluids at oceanic transform faults,” Nature Geoscience, 2014. 7: 757-761. 5. Centre européen de recherche et d’enseignement des géosciences de l’environnement (CNRS / Aix-Marseille Université / IRD / Collège de France). henry@cerege.fr 1. Institut de pharmacologie et de biologie structurale (CNRS / Université Toulouse III-Paul Sabatier). 2. E. Lefrançais et al., “The central domain of IL-33 is cleaved by mast cell proteases for potent activation of group 2 innate lymphoid cells,” PNAS, 2014. 111(43):15502-7.


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