Hyaluronan fragments act as an endogenous danger signal by engaging TLR2

KA Scheibner, MA Lutz, S Boodoo… - The Journal of …, 2006 - journals.aai.org
KA Scheibner, MA Lutz, S Boodoo, MJ Fenton, JD Powell, MR Horton
The Journal of Immunology, 2006journals.aai.org
Upon tissue injury, high mw hyaluronan (HA), a ubiquitously distributed extracellular matrix
component, is broken down into lower mw (LMW) fragments, which in turn activate an innate
immune response. In doing so, LMW HA acts as an endogenous danger signal alerting the
immune system of a breach in tissue integrity. In this report, we demonstrate that LMW HA
activates the innate immune response via TLR-2 in a MyD88-, IL-1R-associated kinase-,
TNFR-associated factor-6-, protein kinase Cζ-, and NF-κB-dependent pathway. Furthermore …
Abstract
Upon tissue injury, high mw hyaluronan (HA), a ubiquitously distributed extracellular matrix component, is broken down into lower mw (LMW) fragments, which in turn activate an innate immune response. In doing so, LMW HA acts as an endogenous danger signal alerting the immune system of a breach in tissue integrity. In this report, we demonstrate that LMW HA activates the innate immune response via TLR-2 in a MyD88-, IL-1R-associated kinase-, TNFR-associated factor-6-, protein kinase Cζ-, and NF-κB-dependent pathway. Furthermore, we show that intact high mw HA can inhibit TLR-2 signaling. Finally, we demonstrate that LMW HA can act as an adjuvant promoting Ag-specific T cell responses in vivo in wild-type but not TLR-2 null mice.
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