Details

Autor(en) / Beteiligte

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

Titel

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.