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It has been unclear which RIPK3-expressing cells are responsible for the anti-inflammatory effect of overall\n                      <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                      deficiency and whether\n                      <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                      deficiency protects against kidney inflammation occurring in the absence of tubular cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used chimeric mice with bone marrow from wild-type and\n                      <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                      -knockout mice to explore RIPK3\u2032s contribution to kidney inflammation in the presence of folic acid\u2013induced acute kidney injury AKI (FA-AKI) or absence of AKI and kidney cell death (as seen in systemic administration of the cytokine TNF-like weak inducer of apoptosis [TWEAK]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tubular and interstitial cell RIPK3 expressions were increased in murine AKI.\n                      <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                      deficiency decreased NF-\n                      <jats:italic toggle=\"yes\">\u03ba<\/jats:italic>\n                      B activation and kidney inflammation in FA-AKI but did not prevent kidney failure. In the chimeric mice, RIPK3-expressing bone marrow\u2013derived cells were required for early inflammation in FA-AKI. The NLRP3 inflammasome was not involved in RIPK3\u2032s proinflammatory effect. Systemic TWEAK administration induced kidney inflammation in wild-type but not\n                      <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                      -deficient mice. In cell cultures, TWEAK increased RIPK3 expression in bone marrow\u2013derived macrophages and tubular cells. RIPK3 mediated TWEAK-induced NF-\n                      <jats:italic toggle=\"yes\">\u03ba<\/jats:italic>\n                      B activation and inflammatory responses in bone marrow\u2013derived macrophages and dendritic cells and in Jurkat T cells; however, in tubular cells, RIPK3 mediated only TWEAK-induced\n                      <jats:italic toggle=\"yes\">Il-6<\/jats:italic>\n                      expression. Furthermore, conditioned media from TWEAK-exposed wild-type macrophages, but not from\n                      <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                      -deficient macrophages, promoted proinflammatory responses in cultured tubular cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RIPK3 mediates kidney inflammation independently from tubular cell death. Specific targeting of bone marrow\u2013derived RIPK3 may limit kidney inflammation without the potential adverse effects of systemic RIPK3 targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021030383","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T14:00:11Z","timestamp":1642600811000},"page":"357-373","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":45,"title":["Bone Marrow\u2013Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury"],"prefix":"10.1681","volume":"33","author":[{"given":"Diego","family":"Martin-Sanchez","sequence":"first","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Red de Investigacion Renal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Guerrero-Mauvecin","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1232-3221","authenticated-orcid":false,"given":"Miguel","family":"Fontecha-Barriuso","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Red de Investigacion Renal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Mendez-Barbero","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia Vascular, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3966-212X","authenticated-orcid":false,"given":"Maria Laura","family":"Saiz","sequence":"additional","affiliation":[{"name":"Translational Immunology Laboratory, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Lopez-Diaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria D.","family":"Sanchez-Ni\u00f1o","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Red de Investigacion Renal, Madrid, Spain"},{"name":"Department of Pharmacology, Universidad Autonoma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Cannata-Ortiz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ruiz-Ortega","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Red de Investigacion Renal, Madrid, Spain"},{"name":"Department of Medicine, Universidad Autonoma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Red de Investigacion Renal, Madrid, Spain"},{"name":"Department of Medicine, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Instituto Reina Sofia de Investigaciones Nefrologicas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-5689","authenticated-orcid":false,"given":"Ana B.","family":"Sanz","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental, Instituto de Investigaci\u00f3n Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Red de Investigacion Renal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,2]]},"reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/ckj\/sfz139","article-title":"Development and internal validation of a prediction model for hospital-acquired acute kidney injury","volume":"14","author":"Martin-Cleary","year":"2019","journal-title":"Clin Kidney J"},{"key":"B2-20250823","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/S0140-6736(11)61454-2","article-title":"Acute kidney 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