T regulatory cell control of bone resorption

Erlangen, Germany -

Although mesenchymal stem cells are primarily known for their differentiation abilities, the first clinical trials, and most likely BLA grantings, will be for immune modulation by these cells in the conditions of graft versus host disease and Crohn's disease.

In the same way that stem cells can modulate the immune system, so the immune system appears to have the ability to alter stem cells. One obvious example is the immune mediated bone marrow aplasia associated with certain viral infections. A more interesting example is how the regulatory, or suppressive components of the immune system may be involved in inhibiting physiological processes that at face value appear to have nothing to do with the immune system. One specific example of this is the recent publication.

Zaiss et al. in a paper (Treg cells suppress osteoclast formation: A new link between the immune system and bone. Arthritis Rheum. 2007 Nov 29;56(12):4104-4112) demonstrated that when Treg cells were mixed with osteoclast progenitor cells and cultured so as to allow cell-to-cell contact, the osteoclast progenitor cells did not differentiate into osteoclasts.

It appeared that CTLA-4 expression on the Treg was essential for inhibition of osteoclast maturation. TGF-b, IL-4, and IL-10 generated by the Treg inhibited osteoclast maturation but not as strongly as CTLA-4. Interestingly, control lymphocytes did not inhibit osteoclast maturation.

This study should prompt investigations into the interaction between other physiological systems and the immune system.