{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:35:26Z","timestamp":1791336926332,"version":"4.3.1"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,9,13]],"date-time":"2015-09-13T00:00:00Z","timestamp":1442102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["2008B037"],"award-info":[{"award-number":["2008B037"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ZonMW","award":["VIDI-16.146.352"],"award-info":[{"award-number":["VIDI-16.146.352"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>LIM\u2010only protein FHL2 is associated with several immune and inflammatory diseases such as arthritis, influenza A virus infection, and lung inflammation. However, the role of FHL2 in macrophage differentiation and in the development of granuloma formation is unknown. Here, we show that expression of FHL2 is induced in mouse bone marrow derived macrophages (BMMs) following stimulation with M2 cytokines such as IL\u20104 and IL\u201010. FHL2\u2010knockout (FHL2\u2010KO) BMMs exhibit a proinflammatory M1 phenotype after LPS treatment and display a reduced anti\u2010inflammatory M2 phenotype following IL\u20104 treatment. Furthermore, thioglycollate\u2010induced migration of macrophages and B cells is enhanced in FHL2\u2010KO mice. To evaluate the importance of FHL2 in the development of pulmonary granuloma formation, FHL2\u2010KO mice were challenged with <jats:italic>Schistosoma mansoni<\/jats:italic> eggs. FHL2\u2010KO mice show an enhanced number of granulomas and display decreased expression of Th2 markers and an exacerbated Th1 type of inflammation, characterized by enhanced expression of neutrophil markers and Th1 cytokines. Furthermore, the expression of barrier proteins is reduced in FHL2\u2010KO lung compared to WT. Collectively, these data identify a previously unrecognized role for FHL2 in the pathogenesis of pulmonary granulomatous inflammation, partly through its effect on macrophage polarization, modulation of the Th1\/Th2 balance and regulation of permeability in lung.<\/jats:p>","DOI":"10.1002\/eji.201545627","type":"journal-article","created":{"date-parts":[[2015,8,24]],"date-time":"2015-08-24T08:30:40Z","timestamp":1440405040000},"page":"3098-3106","source":"Crossref","is-referenced-by-count":12,"title":["LIM\u2010only protein FHL2 regulates experimental pulmonary <i>Schistosoma mansoni<\/i> egg granuloma formation"],"prefix":"10.1002","volume":"45","author":[{"given":"Kondababu","family":"Kurakula","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariska","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"van Eijk","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermelijn H.","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Parasitology Cellular Immunology of Helminths Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlie J.M.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69440-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-07"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2009.01098.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/9.4.371"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri843"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.05.007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.180497"},{"key":"e_1_2_7_10_1","first-page":"619","volume-title":"Histology and Cell Biology: An Introduction to Pathology","author":"Kierszenbaum A.","year":"2002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762006000900034"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2008.951566"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12230"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5438-z"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094931"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00525-14"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081356"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01787.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annerheumdix-2013-20506154"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.308999"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.367"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24921"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903449"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.254"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00107-4"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902009"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082048"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000371"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.07.045"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0241OC"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.4049\/jimmunol.148.7.2283","article-title":"CD4+ Th2 response induced by Schistosoma mansoni eggs develops rapidly, through an early, transient, Th0\u2010like stage","volume":"148","author":"Vella A. 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