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Here, we define a population of resident lung MSCs (luMSCs) that function to regulate the severity of bleomycin injury via modulation of the T-cell response. Bleomycin-induced loss of these endogenous luMSCs and elicited fibrosis (pulmonary fibrosis), inflammation, and pulmonary arterial hypertension (PAH). Replacement of resident stem cells by administration of isolated luMSCs attenuated the bleomycin-associated pathology and mitigated the development of PAH. In addition, luMSC modulated a decrease in numbers of lymphocytes and granulocytes in bronchoalveolar fluid and demonstrated an inhibition of effector T-cell proliferation in vitro. Global gene expression analysis indicated that the luMSCs are a unique stromal population differing from lung fibroblasts in terms of proinflammatory mediators and profibrotic pathways. Our results demonstrate that luMSCs function to protect lung integrity after injury; however, when endogenous MSCs are lost, this function is compromised illustrating the importance of this novel population during lung injury. The definition of this population in vivo in both murine and human pulmonary tissue facilitates the development of a therapeutic strategy directed at the rescue of endogenous cells to facilitate lung repair during injury.<\/jats:p>","DOI":"10.1002\/stem.604","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T21:19:54Z","timestamp":1296767994000},"page":"725-735","source":"Crossref","is-referenced-by-count":127,"title":["The Pathology of Bleomycin-Induced Fibrosis Is Associated with Loss of Resident Lung Mesenchymal Stem Cells That Regulate Effector T-cell Proliferation"],"prefix":"10.1093","volume":"29","author":[{"given":"Du","family":"Jun","sequence":"first","affiliation":[{"name":"Charles C. 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Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA"},{"name":"Department of Medicine,University of Colorado Denver, Aurora, Colorado, USA"},{"name":"Division of Pulmonary, Allergy and Critical Care Medicine,University of Colorado Denver, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children's Hospital, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Meyrick","sequence":"additional","affiliation":[{"name":"Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight","family":"Klemm","sequence":"additional","affiliation":[{"name":"Charles C. 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