4-1BB inhibits myelopoiesis/dendritic cell generation

San Diego, CA -

We at StemCellPatents.com are very interested in trans-disciplinary findings (scientific disciplines are made by humans to make learning easier but the body functions by integration).  One area where scientific disciplines are beginning to overlap more and more is between stem cells and the immune system.  We all know that some types of stem cells, such as mesenchymal stem cells, are immune suppressive.  Mesenchymal stem cells also increase T cell survival.  Additionally, some stem cells, including CD34 hematopoietic stem cells can have a veto-like effect on T cells.  On the other hand immune cells have effects on stem cells.  Just one example of many, if you administer activated peripheral blood mononuclear cells into a recipient, you can actually "reprogram" the bone marrow hematopoietic stem cell compartment to make more neutrophils. 

A recent paper (Lee et al. Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells. Nat Immunol. 2008 Jul 6) describes the effect of the T cell costimulatory molecule 4-1BB, otherwise known as CD137 on hematopoiesis. 

The study found that:

 - the ligand for 4-1BB is found on granulocytic-monocytic progenitors, the myeloid progenitor, and hematopoietic stem cells

-  during activation of myeloid progenitor cells, 4-1BB expression increased

-  knocking out EITHER 4-1BBL or 4-1BB resulted in higher numbers of dendritic cells, as well as myeloid cells

-  in vitro and bone marrow chimeric studies demonstrated that the interaction between 4-1BB and it's ligand suppresses myelopoiesis

This seems VERY INTERESTING since a paper last month said that ligation of 4-1BB actually STIMULATES DENDRITIC CELL FORMATION FROM CD34 cells.

Maybe someone can explain what appears at face value to be a contradiction.