TY - JOUR
T1 - Cutting edge
T2 - Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease
AU - Frisancho-Kiss, Sylvia
AU - Davis, Sarah E.
AU - Nyland, Jennifer F.
AU - Frisancho, J. Augusto
AU - Cihakova, Daniela
AU - Barrett, Masheka A.
AU - Rose, Noel R.
AU - Fairweather, De Lisa
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.178.11.6710
DO - 10.4049/jimmunol.178.11.6710
M3 - Article
C2 - 17513715
AN - SCOPUS:34249811203
SN - 0022-1767
VL - 178
SP - 6710
EP - 6714
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -