Simarro, MariaGiannattasio, GiorgioDe la Fuente, Miguel A.Benarafa, CharafSubramanian, Kulandayan K.Ishizawar, Rumey ChangBalestrieri, BarbaraAndersson, Emma M.Luo, HongboOrduna, AntonioBoyce, JoshuaAnderson, Paul2014-11-052010Simarro, Maria, Giorgio Giannattasio, Miguel A. De la Fuente, Charaf Benarafa, Kulandayan K. Subramanian, Rumey Chang Ishizawar, Barbara Balestrieri, et al. 2010. “Fas-Activated Serine/Threonine Phosphoprotein Promotes Immune-Mediated Pulmonary Inflammation.” The Journal of Immunology 184 (9) (April 2): 5325–5332. doi:10.4049/jimmunol.1000104. http://dx.doi.org/10.4049/jimmunol.1000104.0022-17671550-6606http://nrs.harvard.edu/urn-3:HUL.InstRepos:13350265We 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.en-USJournal Article10.4049/jimmunol.1000104