Dataset Information

Sex-dependent differences in type I IFN-induced natural killer cell activation.

ABSTRACT: Natural killer (NK) cells are important antiviral effector cells and also involved in tumor clearance. NK cells express IFNAR, rendering them responsive to Type I IFNs. To evaluate Type I IFN-mediated modulation of NK cell functions, individual Type I IFNs subtypes were assessed for their ability to activate NK cells. Different Type I IFN subtypes displayed a broad range in the capacity to induce and modulate NK cell activation and degranulation, measured by CD69 and CD107a expression in response to leukemia cell line K562. When including biological sex as a variable in the analysis, transwell co-cultures of NK cells with either male- or female-derived PBMCs or pDCs stimulated with the TLR7/8 agonist CL097 showed that NK cells were more activated by CL097-stimulated cells derived from females. These sex-specific differences were linked to higher CL097-induced IFNα production by pDCs derived from females, indicating an extrinsic sex-specific effect of Type I IFNs on NK cell function. Interestingly, in addition to the extrinsic effect, we also observed NK cell-intrinsic sex differences, as female NK cells displayed higher activation levels after IFNα-stimulation and after co-culture with CL097-stimulated pDCs, suggesting higher activation of IFNα-signaling transduction in female NK cells. Taken together, the results from these studies identify both extrinsic and intrinsic sex-specific differences in Type I IFN-dependent NK cell functions, contributing to a better understanding of sex-specific differences in innate immunity.

SUBMITTER: Pujantell M

PROVIDER: S-EPMC10757368 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sex-dependent differences in type I IFN-induced natural killer cell activation.

Pujantell Maria M Skenteris Nikolaos-Taxiarchis NT Claussen Janna Marieke JM Grünhagel Benjamin B Thiele Rebecca-Jo RJ Altfeld Marcus M

Frontiers in immunology 20231215

Natural killer (NK) cells are important antiviral effector cells and also involved in tumor clearance. NK cells express IFNAR, rendering them responsive to Type I IFNs. To evaluate Type I IFN-mediated modulation of NK cell functions, individual Type I IFNs subtypes were assessed for their ability to activate NK cells. Different Type I IFN subtypes displayed a broad range in the capacity to induce and modulate NK cell activation and degranulation, measured by CD69 and CD107a expression in respons ...[more]

PMID: 38162640

Similar Datasets

Project description: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. 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. 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. 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.

Dataset Information

Sex-dependent differences in type I IFN-induced natural killer cell activation.

Publications

Sex-dependent differences in type I IFN-induced natural killer cell activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets