ADAM10 is required for SCF-induced mast cell migration

• ADAM10 deficiency results in skin and intestinal mast cell hyperplasia.
• Mast cells express ADAM10 at high levels compared to other immune cells.
• ADAM10 deficient mast cells are defective in SCF-, but not IgE-mediated migration.
• ADAM10 expression can be suppressed by TGFβ1 and by IL-10. IL-10 employs STAT3 for this suppressive effect.

A Disintegrin and Metalloproteinase (ADAM)-10 plays critical roles in neuronal migration and distribution. Recently, ADAM10 deletion was shown to disrupt myelopoiesis. We found that inducible deletion of ADAM10 using Mx1-driven Cre recombinase for a period of three weeks resulted in mast cell hyperplasia in the skin, intestine and spleen. Mast cells express surface ADAM10 in vitro and in vivo, at high levels compared to other immune cells tested. ADAM10 is important for mast cell migration, since ADAM10-deficiency reduced c-Kit-mediated migration. As with some mast cell proteases, ADAM10 expression could be altered by the cytokine microenvironment, being inhibited by IL-10 or TGFβ1, but not by several other T cell-derived cytokines. Collectively these data show that the ADAM10 protease is an important factor in mast cell migration and tissue distribution, and can be manipulated by environmental cues.