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IL-6 is produced by multiple peripheral and central cells, and until now, the putative roles of IL-6 from different cell types have been evaluated through conditional cell-specific IL-6 knockout mice. Nevertheless, these mice probably undergo compensatory responses of IL-6 from other cells, which makes it difficult to assess the role of each source of IL-6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To give some insight into this problem, we have produced a novel mouse model: a conditional reversible IL-6 KO mouse (IL6-DIO-KO). By using double-inverted, open-reading-frame (DIO) technology, we created a mouse line with the loss of\n                      <jats:italic>Il6<\/jats:italic>\n                      expression in all cells that can be restored by the action of Cre recombinase. Since microglia are one of the most important sources and targets of IL-6 into the central nervous system, we have recovered microglial\n                      <jats:italic>Il6<\/jats:italic>\n                      expression in IL6-DIO-KO mice through breeding to\n                      <jats:italic>Cx3cr1<\/jats:italic>\n                      -CreER mice and subsequent injection of tamoxifen (TAM) when mice were 10\u201316\u2009weeks old. Then, they were immunized with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG\n                      <jats:sub>35-55<\/jats:sub>\n                      ) 7\u2009weeks after TAM treatment to induce EAE. Clinical symptoms and demyelination, CD3 infiltration, and gliosis in the spinal cord were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL6-DIO-KO mice were resistant to EAE, validating the new model. Restoration of microglial\n                      <jats:italic>Il6<\/jats:italic>\n                      was sufficient to develop a mild version of EAE-related clinical symptoms and neuropathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IL6-DIO-KO mouse is an excellent model to understand in detail the role of specific cellular sources of IL-6 within a recovery-of-function paradigm in EAE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-020-01969-0","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T10:03:38Z","timestamp":1602756218000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A new mouse model to study restoration of interleukin-6 (IL-6) expression in a Cre-dependent manner: microglial IL-6 regulation of experimental autoimmune encephalomyelitis"],"prefix":"10.1186","volume":"17","author":[{"given":"Paula","family":"Sanchis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaya","family":"Fern\u00e1ndez-Gayol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Comes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Escrig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Giralt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Palmiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0921-1122","authenticated-orcid":false,"given":"Juan","family":"Hidalgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"1969_CR1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/S0092-8674(85)80004-0","volume":"41","author":"RD Palmiter","year":"1985","unstructured":"Palmiter RD, Brinster R. 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