Abstract

Mechanism of Action of a MSC Exosome-mediated Therapeutic Activity: Inhibition of IL-17 in Psoriasis

Sai Kiang Lim, Research Director, A*STAR Institute of Medical Biology

Mesenchymal stem/stromal cell (MSC) exosomes are widely known for their potent immunomodulatory properties.  Recently, we reported that when topically applied, MSC exosomes could alleviate IL-17, a key disease driver of psoriasis in the skin of a mouse model of imiquimod (IMQ)-induced psoriasis.  As topically applied MSC exosomes are confined to the stratum corneum, the targets of MSC exosome immunomodulating activity must reside in the stratum corneum.  The psoriatic stratum corneum is known to be rich in two immune components, activated complements and infiltrating neutrophils in Munro microabscesses.  To investigate if topically applied MSC exosomes reduce IL-17 through a mechanism involving complements and neutrophils, we observed for the first time that IL-17 secretion in neutrophils could be induced by C5b9 the terminal complement complex and this induction is inhibited by MSC exosomes.  A neutralizing antibody against CD 59 abolished the exosome-mediated inhibition of IL-17 secretion with a concomitant reduction in C5b9 concentration.  Together these observations demonstrated that topically applied MSC exosomes reduce IL-17 secretion in psoriatic skin by inhibiting formation of activated complement complexes through exosomal CD59 and thereby reducing the induction of IL-17 secretion by neutrophils.