Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression

• DOI: 10.1073/pnas.1016496108
• Publication Date: 2011-07-19T03:35:45Z
• Authors: Laure Guenin-Macé; Florent Carrette; François Asperti-...; Agnès Le Bon; Laxmee Caleechurn; Vincenzo Di Bartolo; Arnaud Fontanet; Georges Bismuth; Caroline Demangel
• Keywords: Homing (biology); Adoptive Cell Transfer

Mycolactone is a macrolide produced by Mycobacterium ulcerans with immunomodulatory properties. Here, we describe that in mouse, mycolactone injection led to massive T-cell depletion peripheral lymph nodes (PLNs) was associated defective expression of L-selectin (CD62-L). Importantly, preexposure impaired the capacity T cells reach PLNs after adoptive transfer, respond chemotactic signals, and expand upon antigenic stimulation vivo. We found mycolactone-induced suppression CD62-L human primary induced rapidly at both mRNA protein levels correlated reduced one miRNA: let-7b. Notably, silencing let-7b sufficient inhibit gene expression. Conversely, its overexpression tended up-regulate counteract effects mycolactone. Our results identify homing as biological process targeted Moreover, they reveal mechanism control involving miRNA