Wednesday, May 18, 2016

PSGL-1, a ligand for the selectin family of receptors, controls T cell immunopathology

The Selectin receptors, L, E and P, control T cell migration. New study in Immunity showed that Selplg-KO T cells (lacking selectin receptor ligand PSGL-1) display enhanced effector differentiation and greater control of chronic viral infection and tumor, though it comes at the expense of tissue pathology.  

In this paper the authors referred to PSGL-1 as checkpoint inhibitor. However, unlike CTLA4 and PD1 deficient mice, Selplg -/- naive mice don't show any abnormality. Interestingly, the authors found that Selplg -/- mice efficiently controlled chronic LCMV infection (C13).

However, this enhanced protection against chronic LCMV infection led to severe tissue pathology.

Additionally, and most likely reason why this paper ended up in Immunity, the authors showed that Selplg -/- mice could better control tumor (Yumm1.5 melanoma cells).

At present it is not clear whether PSGL-1 signaling works as an independent "checkpoint inhibitor" in vivo or modulates functionality of other canonical checkpoint inhibitors such as PD-1 .

David Usharauli

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