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The Effect of Sex-Specific Differences on IL-10^-/- Mouse Colitis Phenotype and Microbiota.

ABSTRACT: Sexual dimorphism is an important factor in understanding various diseases, including inflammatory bowel disease (IBD). While females typically exhibit stronger immune responses, the role of sex in IBD remains unclear. This study aimed to explore the sex-dependent differences and inflammatory susceptibility in the most extensively used IBD mouse model as they developed colitis. We monitored IL10-deficient mice (IL-10^-/-) up to 17 weeks of age and characterized their colonic and fecal inflammatory phenotype, as well as their microbiota changes. Here, we originally identified IL-10^-/- female mice as more prone to developing intestinal inflammation, with an increase in fecal miR-21, and dysbiosis with more detrimental characteristics compared to males. Our findings provide valuable insights into the sex-based differences in the pathophysiology of colitis and emphasize the importance of considering sex in experimental designs. Moreover, this study paves the way for future investigations aiming at addressing sex-related differences for the development of adequate disease models and therapeutic strategies, ideally enabling personalized medicine.

SUBMITTER: Maite CB

PROVIDER: S-EPMC10299321 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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The Effect of Sex-Specific Differences on IL-10<sup>-/-</sup> Mouse Colitis Phenotype and Microbiota.

Maite Casado-Bedmar CB Roy Maryline M Emilie Viennois V

International journal of molecular sciences 20230620 12

Sexual dimorphism is an important factor in understanding various diseases, including inflammatory bowel disease (IBD). While females typically exhibit stronger immune responses, the role of sex in IBD remains unclear. This study aimed to explore the sex-dependent differences and inflammatory susceptibility in the most extensively used IBD mouse model as they developed colitis. We monitored IL10-deficient mice (IL-10<sup>-/-</sup>) up to 17 weeks of age and characterized their colonic and fecal ...[more]

PMID: 37373511

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Project description:BackgroundFollowing viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain-specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-10-/-) model derived from the SvEv mouse, had evidence of increased Mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wild type. MMTV is endemic in several mouse strains as an endogenously encoded Betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut-associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10-/- model.ResultsViral preparations extracted from IL-10-/- weanling stomachs revealed augmented MMTV load compared to the SvEv wild type. Illumina sequencing of the viral genome revealed that the two largest contigs shared 96.4-97.3% identity with the mtv-1 endogenous loci and the MMTV(HeJ) exogenous virus from the C3H mouse. The MMTV sag gene cloned from IL-10-/- spleen encoded the MTV-9 superantigen that preferentially activates T-cell receptor Vβ-12 subsets, which were expanded in the IL-10-/- versus the SvEv colon. Evidence of MMTV cellular immune responses to MMTV Gag peptides was observed in the IL-10-/- splenocytes with amplified interferon-γ production versus the SvEv wild type. To address the hypothesis that MMTV may contribute to colitis, we used HIV reverse transcriptase inhibitors, tenofovir and emtricitabine, and the HIV protease inhibitor, lopinavir boosted with ritonavir, for 12-week treatment versus placebo. The combination antiretroviral therapy with known activity against MMTV was associated with reduced colonic MMTV RNA and improved histological score in IL-10-/- mice, as well as diminished secretion of pro-inflammatory cytokines and modulation of the microbiome associated with colitis.ConclusionsThis study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain-specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis. Video Abstract.

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The Effect of Sex-Specific Differences on IL-10^-/- Mouse Colitis Phenotype and Microbiota.

Publications

The Effect of Sex-Specific Differences on IL-10<sup>-/-</sup> Mouse Colitis Phenotype and Microbiota.

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The Effect of Sex-Specific Differences on IL-10-/- Mouse Colitis Phenotype and Microbiota.

Publications

The Effect of Sex-Specific Differences on IL-10<sup>-/-</sup> Mouse Colitis Phenotype and Microbiota.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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The Effect of Sex-Specific Differences on IL-10^-/- Mouse Colitis Phenotype and Microbiota.