Séminaire externe du vendredi 30 septembre 2011 – Docteur Shukti Chakravarti

Vendredi 30 septembre 2011 à 11 h 00 – À l’invitation de Chantal Pichon

« Lumican and fibromodulin regulate collagen architecture
and host innate immune response: recipes for healthy
connective tissues »

Docteur Shukti Chakravarti

Johns Hopkins University – Department of Medicine
720 Rutland Avenue – Ross Building – Baltimore, Etats-Unis

Lumican and fibromodulin are small leucine-rich repeat proteoglycans (SLRP), widely expressed in many connective tissues, such as the skin, cornea and tendon. These SLRPs bind collagen through their LRR motifs and restrict collagen fibril diameter. The keratin sulfate side chains retain water and regulate inter-fibrillar spacing. Gene-targeted mice deficient in these proteoglycans develop abnormally thick collagen fibrils. In the cornea this causes corneal opacity while in tendons and the skin this leads to biomechanical weakness. Recently we also found that lumican interacts with cell surface proteins to regulate CD14-TLR4 mediated innate immune response. As a result the lumican-deficient mice are hypo-responsive to bacterial lipopolysaccharide endotoxins, but overly sensitive to bacterial infections. Fibromodulin has been found by others to bind and possibly activate complement. Thus, lumican and fibromodulin may have a dual role in collagen architecture and in host immune response. Implications of these functions in health and their imbalances in diseases or therapeutic approaches will be discussed.
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