?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F37796%2F&rft.title=Tissue+specific+Cish+expression+supports+alveolar+macrophage+homeostatic+function&rft.creator=Shoger%2C+Karsen+E.&rft.description=Macrophages+play+critical+roles+in+defense+against+microbes+and+clearance+of+dead+cells%2C+but+also+perform+tissue+specific+functions+in+homeostasis.+Distinct+gene+expression+signatures+in+macrophages+isolated+from+varying+tissues+are+largely+determined+by+environmental+signals.+Specifically%2C+the+lung+is+highly+susceptible+to+environmental+changes%2C+such+as+O2+pressure+and+inhalation+of+particulate+and+microbes.+Alveolar+macrophages+are+shaped+by+the+lung+environment+and+have+critical+tissue-specific+functions+in+initiating+and+resolving+lung+inflammation%2C+and+in+maintaining+lung+structure+via+surfactant+and+lipid+catabolism.+While+research+speculates+lung+specific+factors+form+alveolar+macrophage+phenotype+and+homeostatic+function%2C+the+specific+signals+and+regulators+remain+largely+unknown.+Therefore%2C+we+sought+to+explore+lung+specific+cytokine+signals+and+downstream+signaling+regulators+that+shape+homeostatic+functions+of+alveolar+macrophages.%0D%0AWe+found+Cytokine+Inducible+SH2+Containing+Protein+(Cish)%2C+a+SOCS+family+member+known+to+regulate+the+JAK-STAT5+pathway%2C+is+basally+expressed+in+a+tissue-specific+manner+in+alveolar+macrophages.+Further%2C+we+found+that+the+STAT5+activating+cytokine+GM-CSF+regulates+Cish+expression+in+alveolar+macrophages+and+observed+reduced+alveolar+macrophage+Cish+expression+with+GM-CSF+blockade+in+the+lung.+Cish+knockout+mice+exhibit+enlarged+%E2%80%9Cfoamy%E2%80%9D+alveolar+macrophages%2C+impaired+surfactant+metabolism%2C+and+dysregulated+response+to+GM-CSF%2C+all+hallmarks+of+pulmonary+alveolar+proteinosis.+Thus%2C+we+show+alveolar+macrophage+Cish+expression+is+directly+linked+to+lung+specific+factors%2C+namely+GM-CSF%2C+and+influences+surfactant+homeostasis+in+the+lung%2C+a+critical+homeostatic+function+of+alveolar+macrophages.+%0D%0AThe+lung+is+an+especially+critical+site+of+protection+as+it+is+a+barrier+site+that+is+constantly+exposed+to+inhaled+particulate+and+microbes+and+possesses+a+fragile+structure.+Alveolar+macrophages+act+as+sentinels+in+the+lung%2C+protecting+this+sensitive+tissue+from+challenge+while+maintaining+proper+homeostasis+and+structure.+From+a+public+health+perspective%2C+continuing+to+elucidate+the+specific+mechanisms+by+which+alveolar+macrophages+mediate+lung+homeostasis+is+essential+to+providing+cutting+edge+health+care+and+to+continuing+to+develop+therapeutic+treatments+that+can+provide+cures+instead+of+simply+mitigating+symptoms+of+pulmonary+disease.+Here%2C+we+highlight+one+of+many+yet+to+be+uncovered+regulators+of+lung+homeostasis.&rft.date=2020-01-29&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F37796%2F1%2FShoger_Karsen_MasterThesis_Dec2019.pdf&rft.identifier=++Shoger%2C+Karsen+E.++(2020)+Tissue+specific+Cish+expression+supports+alveolar+macrophage+homeostatic+function.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++