SEARCHOTHERpreclinical research, biomedical research

other·preclinical research, biomedical research, immunology, gastroenterology, endocrinology·PMC10644614

Sex-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb/c mice

Biology of Sex Differences · 8 authors, 3 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This study used male and female Balb/c and CD1d-deficient mice fed a high-fat choline-deficient diet to model steatohepatitis. The central result is that NKT cells protect male mice from severe liver inflammation and fibrosis, but this protective role is negligible in female mice during early disease.

Full summary

843 CHARS

This preclinical study investigated sex-specific roles of NKT cells in diet-induced steatohepatitis using Balb/c and CD1d-deficient mice fed a high-fat choline-deficient diet for 6 weeks. Methods included histology, qPCR for fibrosis and inflammatory genes, and flow cytometry for liver immune cells. Central results showed female mice had milder steatohepatitis than males. In male mice, NKT cells were protective, as CD1d-deficient males exhibited increased fibrosis, inflammation, neutrophilic infiltration, and inflammatory macrophages compared to wild-type males. In contrast, NKT cells had a negligible role in early steatohepatitis in female mice, with similar fibrosis and inflammation despite increased liver damage in CD1d-deficient females. Hepatic type I NKT cell levels were significantly lower in female than male wild-type mice.

STUDY TYPE

other

SPECIALTY

preclinical research

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10644614

Sex-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb/c mice

Biology of Sex Differences

READ THE FULL PAPER

ABSTRACT

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in Western countries, evolving into metabolic dysfunction-associated steatohepatitis (MASH) with a sexual dimorphism. 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. Methods A high fat and choline-deficient (HFCD) diet was used in male and female mice, Balb/c mice or CD1d −/− 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. Results 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 −/− 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 −/− females. Relevant, hepatic type I NKT levels in female Balb/c mice were significantly lower than in male. Conclusions NKT cells exert a protective role against experimental steatohepatitis as HFCD-treated CD1d −/− 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13293-023-00569-w.

CITATION EXPORT

Carlos Cuño-Gómiz, Estefanía de Gregorio, Anna Tutusaus et al.. Sex-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb/c mice. Biology of Sex Differences. (2023). https://doi.org/10.1186/s13293-023-00569-w

AUTHORS

8 · 3 CENTRES

Carlos Cuño-Gómiz, Estefanía de Gregorio, Anna Tutusaus, Patricia Rider, Nuria Andrés-Sánchez, Anna Colell, Albert Morales, Montserrat Marí

1grid.10403.360000000091771775Department of Cell Death and Proliferation, IIBB, CSIC, IDIBAPS, 08036 Barcelona, Spain
2https://ror.org/021018s57grid.5841.80000 0004 1937 0247Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
3grid.121334.60000 0001 2097 0141Institute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, INSERM, 34293 Montpellier, France