The metalloprotease ADAM12 regulates the effector function of human Th17 cells.

ABSTRACT: A key modulator of immune homeostasis, TGF? has an important role in the differentiation of regulatory T cells (Tregs) and IL-17-secreting T cells (Th17). How TGF? regulates these functionally opposing T cell subsets is not well understood. We determined that an ADAM family metalloprotease called ADAM12 is specifically and highly expressed in both Tregs and CCR6+ Th17 cells. ADAM12 is induced in vitro upon differentiation of naïve T cells to Th17 cells or IL-17-secreting Tregs. Remarkably, silencing ADAM12 expression in CCR6+ memory T cells enhances the production of Th17 cytokines, similar to suppressing TGF? signaling. Further, ADAM12 knockdown in naïve human T cells polarized towards Th17/Treg cells, or ectopically expressing RORC, greatly enhances IL-17-secreting cell differentiation, more potently then inhibiting TGF? signals. Together, our findings reveal a novel regulatory role for ADAM12 in Th17 cell differentiation or function and may have implications in regulating their aberrant responses during immune pathologies.

SUBMITTER: Zhou AX 

PROVIDER: S-EPMC3867213 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature