GM-CSF protecting diabetes

Sherbrooke, Quebec -

The immune suppressive activity of mesenchymal and hematopoietic stem cells is well known. An interesting question however is whether activation/mobilization of these cells with pharmacological agents can be used to induce systemic immune modulation? Supporting the possibility of stem cell immune modulation is also the observation not so long ago that CD34 stem cells are found circulating in the lymphatics and can rapidly transform themselves into dendritic cells when needed.

In the recent publication (Gaudreau et al. Granulocyte-macrophage colony-stimulating factor prevents diabetes development in NOD mice by inducing tolerogenic dendritic cells that sustain the suppressive function of CD4+CD25+ regulatory T cells. J Immunol. 2007 Sep 15;179(6):3638-47) administration of the clinically-used hematopoietic-stimulator GM-CSF was demonstrated to protect mice from diabetes.

Protected mice had increased numbers of immature dendritic cells in the spleen. This directly contradicts a previous paper that showed tolerance in the same NOD model was associated with mature dendritic cells.

The authors also demonstrated increased numbers of T regulatory cells.

Splenocytes from protected mice did not have the ability to transfer diabetes into naive recipients, however if the CD11c+ cells were removed from the splenocyte fraction, then the splenocytes were capable of transferring diabetes.

These data suggest that GM-CSF is capable of eliciting a population of immature dendritic cells that dominantly excert tolerogenic properties and that their removel can derepress immunity.

Since tumors secrete large quantities of GM-CSF, it may be interesting to see if patients with cancer can benefit from strategies that either remove the GM-CSF or induce maturation of the immature, tolerogenic dendritic cells.