23 research outputs found
Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis
Aims/hypothesis The innate immune cells, invariant natural
killer T cells (iNKT cells), are implicated in the pathogenesis
of psoriasis, an inflammatory condition associated with
obesity and other metabolic diseases, such as diabetes and
dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an
incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor
agonist. This was independent of change in glycaemic control.
We proposed that this unexpected clinical outcome resulted
from a direct effect of GLP-1 on iNKTcells.
Methods We measured circulating and psoriatic plaque
iNKT cell numbers in two patients with type 2 diabetes
and psoriasis before and after commencing GLP-1 analogue
therapy. In addition, we investigated the in vitro effects of
GLP-1 on iNKT cells and looked for a functional GLP-1
receptor on these cells.
Results The Psoriasis Area and Severity Index improved in
both patients following 6 weeks of GLP-1 analogue
therapy. This was associated with an alteration in iNKT
cell number, with an increased number in the circulation
and a decreased number in psoriatic plaques. The GLP-1
receptor was expressed on iNKT cells, and GLP-1 induced
a dose-dependent inhibition of iNKT cell cytokine secretion,
but not cytolytic degranulation in vitro.
Conclusions/interpretation The clinical effect observed and
the direct interaction between GLP-1 and the immune
system raise the possibility of therapeutic applications for
GLP-1 in inflammatory conditions such as psoriasis