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, DeLisa Fairweather

Research output: Contribution to journalArticle

125 Citations (Scopus)

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
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Mucin-3
Sex Characteristics
Heart Diseases
T-Lymphocytes
Inflammation
Coxsackievirus Infections
Enterovirus
Adaptive Immunity
Regulatory T-Lymphocytes
Innate Immunity
Interleukin-4
Cardiovascular Diseases
Mortality
Incidence
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Frisancho-Kiss, S., Davis, S. E., Nyland, J. F., Frisancho, J. A., Cihakova, D., Barrett, M. A., ... Fairweather, D. (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.

Cutting edge : Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease. / Frisancho-Kiss, Sylvia; Davis, Sarah E.; Nyland, Jennifer F.; Frisancho, J. Augusto; Cihakova, Daniela; Barrett, Masheka A.; Rose, Noel R.; Fairweather, DeLisa.

In: Journal of Immunology, Vol. 178, No. 11, 01.06.2007, p. 6710-6714.

Research output: Contribution to journalArticle

Frisancho-Kiss, S, Davis, SE, Nyland, JF, Frisancho, JA, Cihakova, D, Barrett, MA, Rose, NR & Fairweather, D 2007, 'Cutting edge: Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease', Journal of Immunology, vol. 178, no. 11, pp. 6710-6714.
Frisancho-Kiss S, Davis SE, Nyland JF, Frisancho JA, Cihakova D, Barrett MA et al. Cutting edge: Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease. Journal of Immunology. 2007 Jun 1;178(11):6710-6714.
Frisancho-Kiss, Sylvia ; Davis, Sarah E. ; Nyland, Jennifer F. ; Frisancho, J. Augusto ; Cihakova, Daniela ; Barrett, Masheka A. ; Rose, Noel R. ; Fairweather, DeLisa. / Cutting edge : Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease. In: Journal of Immunology. 2007 ; Vol. 178, No. 11. pp. 6710-6714.
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