The complement regulator CD46 has multiple functions, including modulating the effect of T cells on interleukin 10 (IL-10)-producing Tr1 regulatory T cells. In Science Signaling, Astier and colleagues show that signaling via the T cell antigen receptor (TCR) alters the O-glycosylation patterns of CD46 to induce its ectodomain shedding and liberation of cytoplasmic domains that influence downstream effector functions. Healthy human T cells undergo loss of CD46 O-linked modifications and secrete IL-10, but T cells from patients with relapsing-remitting multiple sclerosis do not undergo similar processing of CD46 and fail to generate Tr1 cells. The authors speculate that O-glycosylation regulates the accessibility of CD46 to the matrix metalloproteinases needed to liberate its ectodomain. What remains unknown is how TCR signaling leads to changes in de novo glycosylation and how this is altered in patients with autoimmunity.

Sci. Signal. 10, eaah6163 (24 October 2017)