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Cutting Edge: Cross-Regulation by TLR4 and T cell Ig Mucin-3 Determines Sex Differences in Inflammatory Heart Disease
Ist Teil von
Journal of Immunology, 2007-06, Vol.178 (11), p.6710-6714
Ort / Verlag
United States: Am Assoc Immnol
Erscheinungsjahr
2007
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
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-gamma 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.