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Fertile women exhibit lower MASLD risk than men, which diminishes post-menopause. While NKT-cell involvement in steatohepatitis is debated, discrepancies may stem from varied mouse strains used, predominantly C57BL6\/J with Th1-dominant responses. Exploration of steatohepatitis, encompassing both genders, using Balb\/c background, with Th2-dominant immune response, and CD1d-deficient mice in the Balb\/c background (lacking Type I and Type II NKT cells) can clarify gender disparities and NKT-cell influence on MASH progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A high fat and choline-deficient (HFCD) diet was used in male and female mice, Balb\/c mice or CD1d\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice in the Balb\/c background that exhibit a Th2-dominant immune response. Liver fibrosis and inflammatory gene expression were measured by qPCR, and histology assessment. NKT cells, T cells, macrophages and neutrophils were assessed by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Female mice displayed milder steatohepatitis after 6 weeks of HFCD, showing reduced liver damage, inflammation, and fibrosis compared to males. Male Balb\/c mice exhibited NKT-cell protection against steatohepatitis whereas CD1d\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      males on HFCD presented decreased hepatoprotection, increased liver fibrosis, inflammation, neutrophilic infiltration, and inflammatory macrophages. In contrast, the NKT-cell role was negligible in early steatohepatitis development in both female mice, as fibrosis and inflammation were similar despite augmented liver damage in CD1d\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      females. Relevant, hepatic type I NKT levels in female Balb\/c mice were significantly lower than in male.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      NKT cells exert a protective role against experimental steatohepatitis as HFCD-treated CD1d\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      males had more severe fibrosis and inflammation than male Balb\/c mice. In females, the HFCD-induced hepatocellular damage and the immune response are less affected by NKT cells on early steatohepatitis progression, underscoring sex-specific NKT-cell influence in MASH development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-023-00569-w","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T07:02:10Z","timestamp":1699945330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sex-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb\/c mice"],"prefix":"10.1186","volume":"14","author":[{"given":"Carlos","family":"Cu\u00f1o-G\u00f3miz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"de Gregorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tutusaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Andr\u00e9s-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-1834","authenticated-orcid":false,"given":"Anna","family":"Colell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-2269","authenticated-orcid":false,"given":"Albert","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6116-3247","authenticated-orcid":false,"given":"Montserrat","family":"Mar\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"issue":"7","key":"569_CR1","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1093\/intimm\/7.7.1157","volume":"7","author":"Y Makino","year":"1995","unstructured":"Makino Y, Kanno R, Ito T, Higashino K, Taniguchi M. 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