Omega-1, a novel immunomodulator with potential to prevent Type 1 diabetes?
Lead Research Organisation:
University of Cambridge
Department Name: Pathology
Abstract
Type 1 diabetes is an autoimmune disease which is increasing dramatically
in incidence in the UK. The reasons behind this increase are unknown but
one explanation is that a reduced exposure to infectious agents may be
responsible.We have previously shown using a mouse model of type 1
diabetes that extracts of a parasite are able to inhibit development of
diabetes in this mouse strain. It is not necessary to have a live
infection to achieve diabetes prevention. Our studies furthermore show
that prevention is achieved by increasing regulation of the immune
response. We have preliminary data showing that a purified product of the
parasite is able to induce a population of cells involved in immune
regulation. We propose to see whether this product can inhibit diabetes in
our mice, whether it can also induce human regulatory cells and dissect
how a single molecule can do this. The importance of this work is that it
may lead to the development of a novel biomodulator that can be used to
prevent diabetes onset in humans.
in incidence in the UK. The reasons behind this increase are unknown but
one explanation is that a reduced exposure to infectious agents may be
responsible.We have previously shown using a mouse model of type 1
diabetes that extracts of a parasite are able to inhibit development of
diabetes in this mouse strain. It is not necessary to have a live
infection to achieve diabetes prevention. Our studies furthermore show
that prevention is achieved by increasing regulation of the immune
response. We have preliminary data showing that a purified product of the
parasite is able to induce a population of cells involved in immune
regulation. We propose to see whether this product can inhibit diabetes in
our mice, whether it can also induce human regulatory cells and dissect
how a single molecule can do this. The importance of this work is that it
may lead to the development of a novel biomodulator that can be used to
prevent diabetes onset in humans.
Technical Summary
Omega-1 is a glycoprotein produced by the helminth Schistosoma mansoni. We find that this glycoprotein can induce Foxp3 expression, a marker of regulatory T cells, in na?ve CD4+T cells from NOD mice. As our previous studies have shown that extracts containing this glycoprotein can prevent diabetes onset in the NOD mouse model of T1D we propose to determine whether Omega-1 induces functional regulatory T cell activity in T cells from both NOD mice and T cells from diabetic patients. We will furthermore characterise the signalling pathways involved when Omega-1 interacts with the immune system. We will additionally determine whether Omega-1 is able to prevent diabetes onset in NOD mice.