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Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin\u2010like growth factor 2 messenger RNA (mRNA)\u2010binding protein 2 (IGF2BP2)\u2010deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. However, the IGF2BP2<jats:sup>\u2212\/\u2212<\/jats:sup> macrophages are refractory to interleukin\u20104 (IL\u20104) induced activation and alleviate cockroach extract induced pulmonary allergic inflammation. Molecular studies indicate that IGF2BP2 switches M1 macrophages to M2 activation by targeting tuberous sclerosis 1 via an N6\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A)\u2010dependent manner. Additionally, it is also shown a signal transducer and activators of transcription 6 (STAT6)\u2010high mobility group AT\u2010hook 2\u2010IGF2BP2\u2010peroxisome proliferator activated receptor\u2010<jats:italic>\u03b3<\/jats:italic> axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases.<\/jats:p>","DOI":"10.1002\/advs.202100209","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T07:44:40Z","timestamp":1620027880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPAR<i>\u03b3<\/i>"],"prefix":"10.1002","volume":"8","author":[{"given":"Xia","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuge","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Hematology Qilu Hospital Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rucheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology Qilu Hospital Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqiang","family":"Xue","sequence":"additional","affiliation":[{"name":"ABLife BioBigData Institute  Wuhan Hubei 430075 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxun","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Genoem Analysis ABLife Inc.  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