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Updated: Jan 30, 2026

Intravital Imaging of the Mouse Popliteal Lymph Node
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Sex Differences in Mouse Popliteal Lymph Nodes.

Riva Dill-Garlow1, KuanHui Ethan Chen2, Ameae M Walker2

  • 1Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, 92521, USA. rdill002@ucr.edu.

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Female mice exhibit stronger immune responses due to higher glycosylation-dependent cell adhesion molecule 1 (Glycam1) expression, which is regulated by Sry and male gonad formation, impacting inflammation.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Genetics

Background:

  • Females generally display more robust immune responses than males, evidenced by differences in inflammation during delayed-type hypersensitivity (DTH) reactions.
  • Investigating the genetic and cellular underpinnings of these sex-based immune differences is crucial for understanding immune system regulation.

Purpose of the Study:

  • To investigate the molecular and cellular mechanisms responsible for sex differences in delayed-type hypersensitivity (DTH) responses.
  • To identify specific genes and pathways that contribute to differential immune reactivity between males and females.

Main Methods:

  • Utilized wildtype and Four Core Genotypes (FCG) mice models to analyze footpad DTH responses.
  • Assessed popliteal lymph node cellularity and gene expression profiles in response to immune stimuli.
  • Examined the impact of castration and Sry gene expression on DTH responses and immune cell populations.

Main Results:

  • Sex chromosome genes showed minimal influence on DTH responses in FCG mice.
  • Glycosylation-dependent cell adhesion molecule 1 (Glycam1) was the only gene significantly differentially expressed between sexes, higher in females.
  • Female lymph nodes had greater cellularity and more memory T cells, while males had more regulatory T cells, with these differences influenced by Sry and gonad development.

Conclusions:

  • Sry expression, through male gonad formation, indirectly suppresses local inflammatory potential.
  • Glycam1 expression facilitates leukocyte trafficking and contributes to enhanced immune responses in females.
  • Sexual dimorphism in immune responses is influenced by gonadal development and Sry, manifesting pre- and post-pubertally.