Research ArticleImmunology

TCR-stimulated changes in cell surface CD46 expression generate type 1 regulatory T cells

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Sci. Signal.  24 Oct 2017:
Vol. 10, Issue 502, eaah6163
DOI: 10.1126/scisignal.aah6163

Receptor processing dampens inflammation

One of the hallmarks of autoimmune diseases, such as multiple sclerosis (MS), is the lack of regulatory T cells to suppress inflammation. Stimulation of the complement regulatory protein CD46 on T cells triggers the conversion of inflammatory effector cells into interleukin-10 (IL-10)–secreting type 1 regulatory T (Tr1) cells, a process that is defective in MS patients. Ni Choileain et al. found that T cell stimulation altered the O-glycosylation status of CD46, changing its mass and enabling its translocation to the immune synapse, the site of T cell activation. The cell surface abundance of CD46 was reduced upon generation of Tr1 cells, which produced IL-10. In contrast, T cells from MS patients showed a reduced change in CD46 abundance and continued to produce the inflammatory cytokine interferon-γ. Together, these data may aid in the design of immunotherapies to treat MS.