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In RA, CTLA4-Ig (abatacept) reduces the inflammatory activity of macrophages by interacting with the costimulatory molecule CD86. The study aimed to investigate the efficacy of CTLA4-Ig treatment to induce an M2 phenotype both in M1-polarised monocyte-derived macrophages (MDMs) obtained from healthy subjects (HS) and in cultured MDMs obtained from active RA patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cultured MDMs were obtained from peripheral blood mononuclear cells of 7 active RA patients and from 10 HS after stimulation with phorbol myristate acetate (5 ng\/mL) for 24 h. HS-MDMs were then stimulated with lipopolysaccharide (LPS, 1 mg\/mL) for 4 h to induce M1-MDMs. M1-MDMs and RA-MDMs were treated with CTLA4-Ig (100 \u03bcM and 500 \u03bcM) for 3, 12, 24, and 48 h. The gene expression of CD80, CD86, and TLR4 (M1 markers); CD163, CD204, and CD206 (surface M2 markers); and MerTK (functional M2 marker) was evaluated by qRT-PCR. The protein synthesis of surface M2 markers was investigated by Western blotting. The statistical analysis was performed by the Wilcoxon\n                      <jats:italic>t<\/jats:italic>\n                      -test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In LPS-induced HS-M1-MDMs, CTLA4-Ig 100 \u03bcM and 500 \u03bcM significantly downregulated the gene expression of M1 markers (3 h\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01 for all molecules; 12 h\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05 for TLR4 and CD86) and significantly upregulated that of M2 markers, primarily after 12 h of treatment (CD163:\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01 and\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05; CD206:\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05 and\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01; CD204:\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05 by 100 mg\/mL). Moreover, in these cells, CTLA4-Ig 500 \u03bcM increased the protein synthesis of surface M2 markers (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Similarly, in RA-MDMs, the CTLA4-Ig treatment significantly downregulated the gene expression of M1 markers at both concentrations primarily after 12 h (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Furthermore, both concentrations of CTLA4-Ig significantly upregulated the gene expression of CD206 (after 3 h of treatment;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), CD163, and MerTK (after 12 h of treatment,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), whereas CD204 gene expression was significantly upregulated by the high concentration of CTLA4-Ig (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). The protein synthesis of all surface markers was increased primarily by CTLA4-Ig 500 \u03bcM, significantly for CD204 and CD206 after 24 h of treatment (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CTLA4-Ig treatment seems to induce the in vitro shift from M1 to M2 macrophages, of both HS-M1-MDMs and RA-MDMs, as observed by the significant downregulation exerted on selected M1 markers and the upregulation of selected M2 markers suggesting an additional mechanism for its modulation of the RA inflammatory process.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-021-02691-9","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T15:02:22Z","timestamp":1640358142000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["CTLA4-Ig treatment induces M1\u2013M2 shift in cultured monocyte-derived macrophages from healthy subjects and rheumatoid arthritis patients"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-0932","authenticated-orcid":false,"given":"Maurizio","family":"Cutolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Soldano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Gotelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Montagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Campitiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Paolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pizzorni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Sulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Tardito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"2691_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","volume":"6","author":"Q Guo","year":"2018","unstructured":"Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. 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