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Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.

Abstract : Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell-intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo-transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell-intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner.
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Submitted on : Friday, January 27, 2017 - 12:07:07 PM
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Orhan Rasid, Ioana Sonya Ciulean, Catherine Fitting, Noelle Doyen, Jean-Marc Cavaillon. Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2016, 197 (6), pp.2444-54. ⟨10.4049/jimmunol.1601040⟩. ⟨pasteur-01447829⟩



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