Cutting edge: Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease

Sylvia Frisancho-Kiss, Sarah E. Davis, Jennifer F. Nyland, J. Augusto Frisancho, Daniela Cihakova, Masheka A. Barrett, Noel R. Rose, De Lisa Fairweather

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Recent clinical studies have reinforced the importance of sex-related differences in the pathogenesis of cardiovascular diseases, with an increased incidence and mortality in men. Similar to humans, male BALB/c mice infected with coxsackievirus B3 (CVB3) develop more severe inflammation in the heart even though viral replication is no greater than in females. We show that TLR4 and IFN-γ levels are significantly elevated and regulatory T cell (Treg) populations significantly reduced in the heart of males following CVB3 infection, whereas females have significantly increased T cell Ig mucin (Tim)-3, IL-4 and Treg. Blocking Tim-3 in males significantly increases inflammation and TLR4 expression while reducing Treg. In contrast, defective TLR4 signaling significantly reduces inflammation while increasing Tim-3 expression. Cross-regulation of TLR4 and Tim-3 occurs during the innate and adaptive immune response. This novel mechanism may help explain why inflammatory heart disease is more severe in males.

Original languageEnglish (US)
Pages (from-to)6710-6714
Number of pages5
JournalJournal of Immunology
Volume178
Issue number11
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Frisancho-Kiss, S., Davis, S. E., Nyland, J. F., Frisancho, J. A., Cihakova, D., Barrett, M. A., Rose, N. R., & Fairweather, D. L. (2007). Cutting edge: Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease. Journal of Immunology, 178(11), 6710-6714. https://doi.org/10.4049/jimmunol.178.11.6710