{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:43:21Z","timestamp":1790808201651,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The alternative activation of M2 macrophages in the lungs has been implicated as a causative agent in pulmonary fibrosis; however, the mechanisms underlying M2 polarization are poorly characterized. In this study, we investigated the role of the ubiquitously expressed Src homology domain\u2013containing tyrosine phosphatase Shp2 in this process. Shp2 inactivation augmented IL-4\u2013mediated M2 polarization in vitro, suggesting that Shp2 regulates macrophage skewing and prevents a bias toward the M2 phenotype. Conditional removal of Shp2 in monocytes\/macrophages with lysozyme M promoter\u2013driven Cre recombinase caused an IL-4\u2013mediated shift toward M2 polarization. Additionally, an increase in arginase activity was detected in Shp2\u2206\/\u2206 mice after i.p. injection of chitin, whereas Shp2-deficient macrophages showed enhanced M2 polarization and protection against schistosome egg\u2013induced schistosomiasis. Furthermore, mutants were more sensitive than control mice to bleomycin-induced inflammation and pulmonary fibrosis. Shp2 was associated with IL-4R\u03b1 and inhibited JAK1\/STAT6 signaling through its phosphatase activity; loss of Shp2 promoted the association of JAK1 with IL-4R\u03b1, which enhanced IL-4\u2013mediated JAK1\/STAT6 activation that resulted in M2 skewing. Taken together, these findings define a role for Shp2 in alveolar macrophages and reveal that Shp2 is required to inhibit the progression of M2-associated pulmonary fibrosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1303463","type":"journal-article","created":{"date-parts":[[2014,8,16]],"date-time":"2014-08-16T01:37:02Z","timestamp":1408153022000},"page":"2801-2811","source":"Crossref","is-referenced-by-count":97,"title":["Myeloid-Specific Disruption of Tyrosine Phosphatase Shp2 Promotes Alternative Activation of Macrophages and Predisposes Mice to Pulmonary Fibrosis"],"prefix":"10.1093","volume":"193","author":[{"given":"Bo","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou , Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou , Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou , Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou , Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou , Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehai","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine , Hangzhou 310058 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou , Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,9,15]]},"reference":[{"key":"2025030707353589700_r1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.immuni.2010.05.007","article-title":"Alternative activation of macrophages: mechanism and 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