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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Frisancho-Kiss, Sylvia; Davis, Sarah E; Nyland, Jennifer F; Frisancho, J Augusto; Cihakova, Daniela; Barrett, Masheka A; Rose, Noel R; Fairweather, Delisa

Published In J Immunol, (2007 Jun 01)

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-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.

PubMed ID: 17513715 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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