Thursday, September 7, 2017

IL-27 protects against autoimmunity through its effect on Tregs

IL-27 is a heterodimeric cytokine composed of the p28 and Ebi3 subunits produced by APCs. It binds to IL-27 receptors (IL 27Rα:gp130) expressed on several cell types, including T lymphocytes. IL-27Ra-/- mice are shown to be highly susceptible to experimental autoimmune encephalomyelitis (EAE), a mouse of human MS. Earlier studies suggested that effect of IL-27 is mediated through its suppression of pro-inflammatory Th17 cells and generation of anti-inflammatory IL-10 producing Tr1 cells.

A new study in PNAS, however, showed that mice with Treg-specific IL-27Rα-deficiency displayed similar susceptibility to EAE as total IL-27Rα-deficient mice pointing to the role of Tregs in mediating IL-27 effect on EAE.

Compared to WT mice, mice with Treg-selective IL-27Rα-deficiency were not able to recover from EAE, a similar trend seen in total IL-27Rα-deficient mice. IL-10 levels were not different between WT and KO littermates.

Furthermore, in contrast to WT mice, injection of "therapeutic" dosage of IL-27 had no effect on EAE dynamics in Treg-selective IL-27Rα-deficient mice. Nor did antibody-blockade of IL-10 diminish effect of IL-27 on WT mice.

These results suggest that in addition to other cell types or even in contrast to other studies, the role of IL-27 in controlling severity of EAE could be solely mediated through its effect on Foxp3+ Tregs.

posted by David Usharauli 


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