RT info:eu-repo/semantics/article T1 Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation A1 Simarro Grande, María A1 Giannattasio, Giorgio A1 Fuente García, Miguel Ángel de la A1 Benarafa, Charaf A1 Subramanian, Kulandayan K. A1 Ishizawar, Rumey A1 Balestrieri, Barbara A1 Andersson, Emma M. A1 Luo, Hongbo R. A1 Orduña Domingo, Antonio A1 Boyce, Joshua K1 Sistema inmunitario-Enfermedades AB We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice (FAST−/−) to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. FAST−/− mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in FAST−/− mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-α and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because FAST−/− neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation. PB American Association of Immunologists SN 0022-1767 YR 2010 FD 2010 LK http://uvadoc.uva.es/handle/10324/9817 UL http://uvadoc.uva.es/handle/10324/9817 LA eng NO J Immunol. 2010; 184(9): 5325–5332. NO Producción Científica DS UVaDOC RD 20-abr-2024