Role for MyD88, TLR2 and TLR9 but not TLR1, TLR4 or TLR6 in experimental autoimmune encephalomyelitis
Miranda-Hernandez, Socorro, Gerlach, Nicole, Fletcher, Julie M., Biros, Erik, Mack, Matthias, Körner, Heinrich, and Baxter, Alan G. (2011) Role for MyD88, TLR2 and TLR9 but not TLR1, TLR4 or TLR6 in experimental autoimmune encephalomyelitis. Journal of Immunology, 187 (2). pp. 791-804.
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The potential roles of TLRs in the cause and pathogenesis of autoimmune CNS inflammation remain contentious. In this study, we examined the effects of targeted deletions of TLR1, TLR2, TLR4, TLR6, TLR9, and MyD88 on the induction of myelin oligodendrocyte glycoprotein 35–55 (MOG35–55) peptide/CFA/pertussis toxin-induced autoimmune encephalomyelitis. Although C57BL/6.Tlr1−/−, C57BL/6.Tlr4−/− and C57BL/6.Tlr6−/− mice showed normal susceptibility to disease, signs were alleviated in female C57BL/6.Tlr2−/− and C57BL/6.Tlr9−/− mice and C57BL/6.Tlr2/9−/− mice of both sexes. C57BL/6.Myd88−/− mice were completely protected. Lower clinical scores were associated with reduced leukocyte infiltrates. These results were confirmed by passive adoptive transfer of disease into female C57BL/6.Tlr2−/− and C57BL/6.Tlr9−/− mice, where protection in the absence of TLR2 was associated with fewer infiltrating CD4+ cells in the CNS, reduced prevalence of detectable circulating IL-6, and increased proportions of central (CD62L+) CD4+CD25+Foxp3+ regulatory T cells. These results provide a potential molecular mechanism for the observed effects of TLR signaling on the severity of autoimmune CNS inflammation.
|Item Type:||Article (Refereed Research - C1)|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%|
|Deposited On:||30 Jun 2011 12:42|
|Last Modified:||19 Jun 2013 01:39|
Last 12 Months: 1
|Citation Counts with External Providers:||Web of Science: 9|
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