Sex differences in EAE reveal common and distinct cellular and molecular components

Jack Wiedrick, Roberto Meza-Romero, Grant Gerstner, Hilary Seifert, Priya Chaudhary, Ashley Headrick, Gail Kent, Ashley Maestas, Halina Offner, Arthur A. Vandenbark

Research output: Contribution to journalArticlepeer-review

Abstract

Experimental autoimmune encephalomyelitis (EAE) is commonly used as an animal model for evaluating clinical, histological and immunological processes potentially relevant to the human disease multiple sclerosis (MS), for which the mode of disease induction remains largely unknown. An important caveat for interpreting EAE processes in mice is the inflammatory effect of immunization with myelin peptides emulsified in Complete Freund's Adjuvant (CFA), often followed by additional injections of pertussis toxin (Ptx) in some strains to induce EAE. The current study evaluated clinical, histological, cellular (spleen), and chemokine-driven processes in spinal cords of male vs. female C57BL/6 mice that were immunized with mouse (m)MOG-35-55/CFA/Ptx to induce EAE; immunized with saline/CFA/Ptx only (CFA, no EAE); or were untreated (Naïve, no EAE). Analysis of response curves utilized a rigorous and sophisticated methodology to parse and characterize the effects of EAE and adjuvant alone vs. the Naive baseline responses. The results demonstrated stronger pro-inflammatory responses of immune cells and their associated cytokines, chemokines, and receptors in male vs. female CFA and EAE mice that appeared to be offset partially by increased percentages of male anti-inflammatory, regulatory and checkpoint T cell, B cell, and monocyte/macrophage subsets. These sex differences in peripheral immune responses may explain the reduced cellular infiltration and differing chemokine profiles in the Central Nervous System (CNS) of male vs. female CFA immunized mice and the reduced CNS infiltration and demyelination observed in male vs. female EAE groups of mice that ultimately resulted in the same clinical EAE disease severity in both sexes. Our findings suggest EAE disease severity is governed not only by the degree of CNS infiltration and demyelination, but also by the balance of pro-inflammatory vs. regulatory cell types and their secreted cytokines and chemokines.

Original languageEnglish (US)
Article number104242
JournalCellular Immunology
Volume359
DOIs
StatePublished - Jan 2021

Keywords

  • B and T cells
  • Central Nervous System (CNS)
  • Complete Freund's Adjuvant (CFA)
  • Cytokine/chemokines
  • Experimental autoimmune encephalomyelitis (EAE)
  • Inflammation
  • Macrophage migration inhibitory factor (MIF)
  • Macrophages/monocytes
  • Multiple sclerosis (MS)
  • Pertussis toxin (PTx)
  • Sex differences

ASJC Scopus subject areas

  • Immunology

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